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CMS sticks with E/M pay plan over some objections
The Trump administration is sticking with a plan to boost certain Medicare pay for many primary care and other specialties focused heavily on office visits while lowering that for other groups to balance these increased costs.
On Aug. 4, the Centers for Medicare & Medicaid Services posted on the Federal Register draft versions of two of its major annual payment measures: the physician fee schedule and the payment rule for hospital outpatient and ambulatory surgery center services. On Aug. 3, the CMS informally posted a copy of the physician fee schedule on its own website, allowing medical groups to begin reading the more than 1,300-page rule.
Federal officials normally use annual Medicare payment rules to make many revisions to policies as well as adjust reimbursement.
The draft 2021 physician fee schedule, for example, calls for broadening the authority of clinicians other than physicians to authorize testing of people enrolled in Medicare.
The CMS intends to allow nurse practitioners, physician assistants, and certain other health care professionals to more widely supervise diagnostic psychological and neuropsychological tests.
The draft 2021 hospital outpatient rule proposes a gradual changeover to allow more procedures to be performed on an outpatient basis. This shift could save money for Medicare as well as for the people enrolled in the giant federal health program who need these services, the CMS explained.
Medicare would begin with a change in status for almost 300 musculoskeletal-related services, making them eligible for payment in the hospital outpatient setting when appropriate, CMS wrote in a fact sheet.
The initial reaction to Medicare’s proposed 2021 rules centered on its planned redistribution of funds among medical specialties. The CMS had outlined this plan last year. It is part of longstanding efforts to boost pay for primary care specialists and other physicians whose practice centers more around office visits than procedures.
There is broad support in health policy circles for raising pay for these specialties, but there also are strong objections to the cuts the CMS plans to offset the cost of rising pay for some fields.
Susan R. Bailey, MD, president of the American Medical Association, addressed both of these ideas in an AMA news release on the proposed 2021 physician fee schedule. The increase in pay for office visits, covered under evaluation and management services (E/M), stems from recommendations on resource costs from the AMA/Specialty Society RVS Update Committee, Dr. Bailey said.
“Unfortunately, these office visit payment increases, and a multitude of other new CMS proposed payment increases, are required by statute to be offset by payment reductions to other services, through an unsustainable reduction of nearly 11% to the Medicare conversion factor,” Dr. Bailey explained.
In the news release, Dr. Bailey asked Congress to waive Medicare’s budget-neutrality requirements to allow increases without the cuts.
“Physicians are already experiencing substantial economic hardships due to COVID-19, so these pay cuts could not come at a worse time,” she said.
Winners and losers
The CMS details the possible winners and losers in its payment reshuffle in Table 90 of the proposed 2021 physician fee schedule. In the proposed rule, CMS notes in the draft that these figures are based upon estimates of aggregate allowed charges across all services furnished by physicians and other clinicians.
Specialties in line for increases under the 2021 draft rule include allergy/immunology (9%), endocrinology (17%), family practice (13%), geriatrics (4%), hematology/oncology (14%), internal medicine (4%), physician assistants (8%), psychiatry (8%), rheumatology (16%), and urology (8%).
In line for cuts would be anesthesiology (–8%), cardiac surgery (–9%), emergency medicine (–6%), gastroenterology (–5%), general surgery (–7%), infectious disease (–4%), neurosurgery (–7%), physical/occupational therapy (–9%), plastic surgery (–7%), and radiology (–11%).
An umbrella group, the Surgical Care Coalition, had a quick statement ready about the CMS proposal. Writing on behalf of the group was David B. Hoyt, MD, executive director of the American College of Surgeons.
“Today’s proposed rule ignores both patients and the surgeons who care for them. The middle of a pandemic is no time for cuts to any form of health care, but today’s announcement moves ahead as if nothing has changed,” Dr. Hoyt said in the statement. “The Surgical Care Coalition believes no physician should see payment cuts that will reduce patients’ access to care.”
Making a similar request Aug. 4 in a unified statement were the American Physical Therapy Association (APTA), the American Occupational Therapy Association (AOTA), and the American Speech-Language-Hearing Association (ASHA).
“Our organizations call on Congress and CMS to advance well-reasoned fee schedule payment policies and waive budget neutrality,” the groups said.
A version of this article originally appeared on Medscape.com.
We all agree that E/M services have been undercompensated for many years and applaud CMS for increasing their reimbursements, but this does not mean that endoscopic services are suddenly less valuable as a result. Nor does it mean that the work required to perform endoscopic services has declined.
Lawrence R. Kosinski, MD, MBA, AGAF, is the chief medical officer at SonarMD, Chicago. He is also an associate editor for GI & Hepatology News.
We all agree that E/M services have been undercompensated for many years and applaud CMS for increasing their reimbursements, but this does not mean that endoscopic services are suddenly less valuable as a result. Nor does it mean that the work required to perform endoscopic services has declined.
Lawrence R. Kosinski, MD, MBA, AGAF, is the chief medical officer at SonarMD, Chicago. He is also an associate editor for GI & Hepatology News.
We all agree that E/M services have been undercompensated for many years and applaud CMS for increasing their reimbursements, but this does not mean that endoscopic services are suddenly less valuable as a result. Nor does it mean that the work required to perform endoscopic services has declined.
Lawrence R. Kosinski, MD, MBA, AGAF, is the chief medical officer at SonarMD, Chicago. He is also an associate editor for GI & Hepatology News.
The Trump administration is sticking with a plan to boost certain Medicare pay for many primary care and other specialties focused heavily on office visits while lowering that for other groups to balance these increased costs.
On Aug. 4, the Centers for Medicare & Medicaid Services posted on the Federal Register draft versions of two of its major annual payment measures: the physician fee schedule and the payment rule for hospital outpatient and ambulatory surgery center services. On Aug. 3, the CMS informally posted a copy of the physician fee schedule on its own website, allowing medical groups to begin reading the more than 1,300-page rule.
Federal officials normally use annual Medicare payment rules to make many revisions to policies as well as adjust reimbursement.
The draft 2021 physician fee schedule, for example, calls for broadening the authority of clinicians other than physicians to authorize testing of people enrolled in Medicare.
The CMS intends to allow nurse practitioners, physician assistants, and certain other health care professionals to more widely supervise diagnostic psychological and neuropsychological tests.
The draft 2021 hospital outpatient rule proposes a gradual changeover to allow more procedures to be performed on an outpatient basis. This shift could save money for Medicare as well as for the people enrolled in the giant federal health program who need these services, the CMS explained.
Medicare would begin with a change in status for almost 300 musculoskeletal-related services, making them eligible for payment in the hospital outpatient setting when appropriate, CMS wrote in a fact sheet.
The initial reaction to Medicare’s proposed 2021 rules centered on its planned redistribution of funds among medical specialties. The CMS had outlined this plan last year. It is part of longstanding efforts to boost pay for primary care specialists and other physicians whose practice centers more around office visits than procedures.
There is broad support in health policy circles for raising pay for these specialties, but there also are strong objections to the cuts the CMS plans to offset the cost of rising pay for some fields.
Susan R. Bailey, MD, president of the American Medical Association, addressed both of these ideas in an AMA news release on the proposed 2021 physician fee schedule. The increase in pay for office visits, covered under evaluation and management services (E/M), stems from recommendations on resource costs from the AMA/Specialty Society RVS Update Committee, Dr. Bailey said.
“Unfortunately, these office visit payment increases, and a multitude of other new CMS proposed payment increases, are required by statute to be offset by payment reductions to other services, through an unsustainable reduction of nearly 11% to the Medicare conversion factor,” Dr. Bailey explained.
In the news release, Dr. Bailey asked Congress to waive Medicare’s budget-neutrality requirements to allow increases without the cuts.
“Physicians are already experiencing substantial economic hardships due to COVID-19, so these pay cuts could not come at a worse time,” she said.
Winners and losers
The CMS details the possible winners and losers in its payment reshuffle in Table 90 of the proposed 2021 physician fee schedule. In the proposed rule, CMS notes in the draft that these figures are based upon estimates of aggregate allowed charges across all services furnished by physicians and other clinicians.
Specialties in line for increases under the 2021 draft rule include allergy/immunology (9%), endocrinology (17%), family practice (13%), geriatrics (4%), hematology/oncology (14%), internal medicine (4%), physician assistants (8%), psychiatry (8%), rheumatology (16%), and urology (8%).
In line for cuts would be anesthesiology (–8%), cardiac surgery (–9%), emergency medicine (–6%), gastroenterology (–5%), general surgery (–7%), infectious disease (–4%), neurosurgery (–7%), physical/occupational therapy (–9%), plastic surgery (–7%), and radiology (–11%).
An umbrella group, the Surgical Care Coalition, had a quick statement ready about the CMS proposal. Writing on behalf of the group was David B. Hoyt, MD, executive director of the American College of Surgeons.
“Today’s proposed rule ignores both patients and the surgeons who care for them. The middle of a pandemic is no time for cuts to any form of health care, but today’s announcement moves ahead as if nothing has changed,” Dr. Hoyt said in the statement. “The Surgical Care Coalition believes no physician should see payment cuts that will reduce patients’ access to care.”
Making a similar request Aug. 4 in a unified statement were the American Physical Therapy Association (APTA), the American Occupational Therapy Association (AOTA), and the American Speech-Language-Hearing Association (ASHA).
“Our organizations call on Congress and CMS to advance well-reasoned fee schedule payment policies and waive budget neutrality,” the groups said.
A version of this article originally appeared on Medscape.com.
The Trump administration is sticking with a plan to boost certain Medicare pay for many primary care and other specialties focused heavily on office visits while lowering that for other groups to balance these increased costs.
On Aug. 4, the Centers for Medicare & Medicaid Services posted on the Federal Register draft versions of two of its major annual payment measures: the physician fee schedule and the payment rule for hospital outpatient and ambulatory surgery center services. On Aug. 3, the CMS informally posted a copy of the physician fee schedule on its own website, allowing medical groups to begin reading the more than 1,300-page rule.
Federal officials normally use annual Medicare payment rules to make many revisions to policies as well as adjust reimbursement.
The draft 2021 physician fee schedule, for example, calls for broadening the authority of clinicians other than physicians to authorize testing of people enrolled in Medicare.
The CMS intends to allow nurse practitioners, physician assistants, and certain other health care professionals to more widely supervise diagnostic psychological and neuropsychological tests.
The draft 2021 hospital outpatient rule proposes a gradual changeover to allow more procedures to be performed on an outpatient basis. This shift could save money for Medicare as well as for the people enrolled in the giant federal health program who need these services, the CMS explained.
Medicare would begin with a change in status for almost 300 musculoskeletal-related services, making them eligible for payment in the hospital outpatient setting when appropriate, CMS wrote in a fact sheet.
The initial reaction to Medicare’s proposed 2021 rules centered on its planned redistribution of funds among medical specialties. The CMS had outlined this plan last year. It is part of longstanding efforts to boost pay for primary care specialists and other physicians whose practice centers more around office visits than procedures.
There is broad support in health policy circles for raising pay for these specialties, but there also are strong objections to the cuts the CMS plans to offset the cost of rising pay for some fields.
Susan R. Bailey, MD, president of the American Medical Association, addressed both of these ideas in an AMA news release on the proposed 2021 physician fee schedule. The increase in pay for office visits, covered under evaluation and management services (E/M), stems from recommendations on resource costs from the AMA/Specialty Society RVS Update Committee, Dr. Bailey said.
“Unfortunately, these office visit payment increases, and a multitude of other new CMS proposed payment increases, are required by statute to be offset by payment reductions to other services, through an unsustainable reduction of nearly 11% to the Medicare conversion factor,” Dr. Bailey explained.
In the news release, Dr. Bailey asked Congress to waive Medicare’s budget-neutrality requirements to allow increases without the cuts.
“Physicians are already experiencing substantial economic hardships due to COVID-19, so these pay cuts could not come at a worse time,” she said.
Winners and losers
The CMS details the possible winners and losers in its payment reshuffle in Table 90 of the proposed 2021 physician fee schedule. In the proposed rule, CMS notes in the draft that these figures are based upon estimates of aggregate allowed charges across all services furnished by physicians and other clinicians.
Specialties in line for increases under the 2021 draft rule include allergy/immunology (9%), endocrinology (17%), family practice (13%), geriatrics (4%), hematology/oncology (14%), internal medicine (4%), physician assistants (8%), psychiatry (8%), rheumatology (16%), and urology (8%).
In line for cuts would be anesthesiology (–8%), cardiac surgery (–9%), emergency medicine (–6%), gastroenterology (–5%), general surgery (–7%), infectious disease (–4%), neurosurgery (–7%), physical/occupational therapy (–9%), plastic surgery (–7%), and radiology (–11%).
An umbrella group, the Surgical Care Coalition, had a quick statement ready about the CMS proposal. Writing on behalf of the group was David B. Hoyt, MD, executive director of the American College of Surgeons.
“Today’s proposed rule ignores both patients and the surgeons who care for them. The middle of a pandemic is no time for cuts to any form of health care, but today’s announcement moves ahead as if nothing has changed,” Dr. Hoyt said in the statement. “The Surgical Care Coalition believes no physician should see payment cuts that will reduce patients’ access to care.”
Making a similar request Aug. 4 in a unified statement were the American Physical Therapy Association (APTA), the American Occupational Therapy Association (AOTA), and the American Speech-Language-Hearing Association (ASHA).
“Our organizations call on Congress and CMS to advance well-reasoned fee schedule payment policies and waive budget neutrality,” the groups said.
A version of this article originally appeared on Medscape.com.
Top AGA Community patient cases
Physicians with difficult patient scenarios regularly bring their questions to the AGA Community (https://community.gastro.org) to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses. The upgraded networking platform now features a newsfeed for difficult patient scenarios and regularly scheduled Roundtable discussions with experts in the field.
In case you missed it, here are some clinical discussions and Roundtables in the newsfeed this month:
- AGA Clinical Practice Update on Pancreas Cancer Screening in High-Risk Individuals: Expert Review (https://community.gastro.org/posts/22199)
- Establishing an acute colitis pathway (https://community.gastro.org/posts/22171)
- Preprocedure COVID testing (https://community.gastro.org/posts/22164)
- Patient case: Gastroesophageal varices (https://community.gastro.org/posts/22098)
- Patient case: IBD with intra-abdominal sepsis (https://community.gastro.org/posts/22055)
- Patient case: Hypervascular pancreatic parenchyma (https://community.gastro.org/posts/22039)
Roundtables (https://community.gastro.org/discussions/)
- Windows on Clinical GI
- Clinical Challenges in IBD: Ulcerative colitis and a fistula
- GI COVID-19 Connection: Implementing an effective long-term telehealth program in a post-COVID world
View all upcoming Roundtables in the community at https://community.gastro.org/discussions.
Physicians with difficult patient scenarios regularly bring their questions to the AGA Community (https://community.gastro.org) to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses. The upgraded networking platform now features a newsfeed for difficult patient scenarios and regularly scheduled Roundtable discussions with experts in the field.
In case you missed it, here are some clinical discussions and Roundtables in the newsfeed this month:
- AGA Clinical Practice Update on Pancreas Cancer Screening in High-Risk Individuals: Expert Review (https://community.gastro.org/posts/22199)
- Establishing an acute colitis pathway (https://community.gastro.org/posts/22171)
- Preprocedure COVID testing (https://community.gastro.org/posts/22164)
- Patient case: Gastroesophageal varices (https://community.gastro.org/posts/22098)
- Patient case: IBD with intra-abdominal sepsis (https://community.gastro.org/posts/22055)
- Patient case: Hypervascular pancreatic parenchyma (https://community.gastro.org/posts/22039)
Roundtables (https://community.gastro.org/discussions/)
- Windows on Clinical GI
- Clinical Challenges in IBD: Ulcerative colitis and a fistula
- GI COVID-19 Connection: Implementing an effective long-term telehealth program in a post-COVID world
View all upcoming Roundtables in the community at https://community.gastro.org/discussions.
Physicians with difficult patient scenarios regularly bring their questions to the AGA Community (https://community.gastro.org) to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses. The upgraded networking platform now features a newsfeed for difficult patient scenarios and regularly scheduled Roundtable discussions with experts in the field.
In case you missed it, here are some clinical discussions and Roundtables in the newsfeed this month:
- AGA Clinical Practice Update on Pancreas Cancer Screening in High-Risk Individuals: Expert Review (https://community.gastro.org/posts/22199)
- Establishing an acute colitis pathway (https://community.gastro.org/posts/22171)
- Preprocedure COVID testing (https://community.gastro.org/posts/22164)
- Patient case: Gastroesophageal varices (https://community.gastro.org/posts/22098)
- Patient case: IBD with intra-abdominal sepsis (https://community.gastro.org/posts/22055)
- Patient case: Hypervascular pancreatic parenchyma (https://community.gastro.org/posts/22039)
Roundtables (https://community.gastro.org/discussions/)
- Windows on Clinical GI
- Clinical Challenges in IBD: Ulcerative colitis and a fistula
- GI COVID-19 Connection: Implementing an effective long-term telehealth program in a post-COVID world
View all upcoming Roundtables in the community at https://community.gastro.org/discussions.
FDA expands remdesivir use for all COVID-19 hospitalized patients
An EUA of remdesivir issued in May allowed the drug to be used only for patients with severe COVID-19, specifically, COVID-19 patients with low blood oxygen levels or who need oxygen therapy or mechanical ventilation.
“Today, based on the Agency’s ongoing review of the EUA, including its review of the totality of scientific information now available, the FDA has determined that it is reasonable to believe Veklury may be effective for the treatment of suspected or laboratory-confirmed COVID-19 in all hospitalized adult and pediatric patients,” the FDA news release about the expanded EUA said. “The Agency’s review has also concluded that the known and potential benefits of Veklury outweigh the known and potential risks for these uses.”
‘Further evaluation’ needed
The EUA expansion is partially based on the results of a randomized, open-label trial that Gilead Sciences, remdesivir’s manufacturer, conducted at multiple sites.
The trial showed that a 5-day course of remdesivir was associated with statistically significant improvement among patients hospitalized with moderate COVID-19 in comparison with those receiving standard care. However, patients who were randomly assigned to a receive longer, 10-day remdesivir course had not improved significantly 11 days after treatment started, compared with those who received standard care.
Results with remdesivir in this trial and in two previously reported randomized trials varied, “raising the question of whether the discrepancies are artifacts of study design choices, including patient populations, or whether the drug is less efficacious than hoped,” wrote Erin K. McCreary, PharmD, and Derek C. Angus, MD, MPH, with the University of Pittsburgh School of Medicine, in an editorial that accompanied publication of the trials in JAMA.
Angus previously expressed concern that expanding remdesivir’s EUA could “interrupt or thwart efforts to execute the needed RCTs [randomized controlled trials].
“We think there really needs to be further evaluation of remdesivir in large-scale RCTs adequately powered to understand in which patients, at which dose, given at which point in the course of illness leads to what concrete and tangible improvement in clinical outcomes,” he told Medscape Medical News.
“At this point, remdesivir definitely holds promise, but given the cost to produce and distribute the drug, it seems crucial to know with more certainty how best to use it,” Angus said.
The EUA expansion is also partially based on results from a randomized, double-blind, placebo-controlled clinical trial that the National Institutes of Allergy and Infectious Diseases conducted. In that trial, there was a statistically significant reduction in median recovery time and higher odds of clinical improvement after 2 weeks for hospitalized patients who received remdesivir.
For hospitalized patients with mild to moderate disease, the results were consistent with the overall study results but were not statistically significant.
This article first appeared on Medscape.com.
An EUA of remdesivir issued in May allowed the drug to be used only for patients with severe COVID-19, specifically, COVID-19 patients with low blood oxygen levels or who need oxygen therapy or mechanical ventilation.
“Today, based on the Agency’s ongoing review of the EUA, including its review of the totality of scientific information now available, the FDA has determined that it is reasonable to believe Veklury may be effective for the treatment of suspected or laboratory-confirmed COVID-19 in all hospitalized adult and pediatric patients,” the FDA news release about the expanded EUA said. “The Agency’s review has also concluded that the known and potential benefits of Veklury outweigh the known and potential risks for these uses.”
‘Further evaluation’ needed
The EUA expansion is partially based on the results of a randomized, open-label trial that Gilead Sciences, remdesivir’s manufacturer, conducted at multiple sites.
The trial showed that a 5-day course of remdesivir was associated with statistically significant improvement among patients hospitalized with moderate COVID-19 in comparison with those receiving standard care. However, patients who were randomly assigned to a receive longer, 10-day remdesivir course had not improved significantly 11 days after treatment started, compared with those who received standard care.
Results with remdesivir in this trial and in two previously reported randomized trials varied, “raising the question of whether the discrepancies are artifacts of study design choices, including patient populations, or whether the drug is less efficacious than hoped,” wrote Erin K. McCreary, PharmD, and Derek C. Angus, MD, MPH, with the University of Pittsburgh School of Medicine, in an editorial that accompanied publication of the trials in JAMA.
Angus previously expressed concern that expanding remdesivir’s EUA could “interrupt or thwart efforts to execute the needed RCTs [randomized controlled trials].
“We think there really needs to be further evaluation of remdesivir in large-scale RCTs adequately powered to understand in which patients, at which dose, given at which point in the course of illness leads to what concrete and tangible improvement in clinical outcomes,” he told Medscape Medical News.
“At this point, remdesivir definitely holds promise, but given the cost to produce and distribute the drug, it seems crucial to know with more certainty how best to use it,” Angus said.
The EUA expansion is also partially based on results from a randomized, double-blind, placebo-controlled clinical trial that the National Institutes of Allergy and Infectious Diseases conducted. In that trial, there was a statistically significant reduction in median recovery time and higher odds of clinical improvement after 2 weeks for hospitalized patients who received remdesivir.
For hospitalized patients with mild to moderate disease, the results were consistent with the overall study results but were not statistically significant.
This article first appeared on Medscape.com.
An EUA of remdesivir issued in May allowed the drug to be used only for patients with severe COVID-19, specifically, COVID-19 patients with low blood oxygen levels or who need oxygen therapy or mechanical ventilation.
“Today, based on the Agency’s ongoing review of the EUA, including its review of the totality of scientific information now available, the FDA has determined that it is reasonable to believe Veklury may be effective for the treatment of suspected or laboratory-confirmed COVID-19 in all hospitalized adult and pediatric patients,” the FDA news release about the expanded EUA said. “The Agency’s review has also concluded that the known and potential benefits of Veklury outweigh the known and potential risks for these uses.”
‘Further evaluation’ needed
The EUA expansion is partially based on the results of a randomized, open-label trial that Gilead Sciences, remdesivir’s manufacturer, conducted at multiple sites.
The trial showed that a 5-day course of remdesivir was associated with statistically significant improvement among patients hospitalized with moderate COVID-19 in comparison with those receiving standard care. However, patients who were randomly assigned to a receive longer, 10-day remdesivir course had not improved significantly 11 days after treatment started, compared with those who received standard care.
Results with remdesivir in this trial and in two previously reported randomized trials varied, “raising the question of whether the discrepancies are artifacts of study design choices, including patient populations, or whether the drug is less efficacious than hoped,” wrote Erin K. McCreary, PharmD, and Derek C. Angus, MD, MPH, with the University of Pittsburgh School of Medicine, in an editorial that accompanied publication of the trials in JAMA.
Angus previously expressed concern that expanding remdesivir’s EUA could “interrupt or thwart efforts to execute the needed RCTs [randomized controlled trials].
“We think there really needs to be further evaluation of remdesivir in large-scale RCTs adequately powered to understand in which patients, at which dose, given at which point in the course of illness leads to what concrete and tangible improvement in clinical outcomes,” he told Medscape Medical News.
“At this point, remdesivir definitely holds promise, but given the cost to produce and distribute the drug, it seems crucial to know with more certainty how best to use it,” Angus said.
The EUA expansion is also partially based on results from a randomized, double-blind, placebo-controlled clinical trial that the National Institutes of Allergy and Infectious Diseases conducted. In that trial, there was a statistically significant reduction in median recovery time and higher odds of clinical improvement after 2 weeks for hospitalized patients who received remdesivir.
For hospitalized patients with mild to moderate disease, the results were consistent with the overall study results but were not statistically significant.
This article first appeared on Medscape.com.
Beyond microcephaly: Zika-affected children near school age
In 2020, “the virus” has come to mean one thing: SARS-CoV-2. But just a few years ago, Zika had the world's attention, as one news report after another described children with microcephaly born to women who'd been infected while pregnant.
It can be difficult for physicians to determine whether a birth defect is the result of Zika. Most infections have few or no symptoms, and mothers may not know if they’ve been exposed. Karin Nielsen, MD, remembers one child in particular, a 9-month-old boy born with microcephaly whose parents brought the infant to her in 2018 because he had started having seizures.
The child was born in Mexico in 2017, when the Zika virus was still known to be circulating in the Americas, said Dr. Nielsen, a pediatric infectious disease specialist at the University of California, Los Angeles. Brain imaging revealed calcifications and other signs in the boy’s brain that were consistent with exposure. But his mother said she was never sick during pregnancy.
Because Zika is transmitted not just via mosquito and from mother to fetus but also sexually, Dr. Nielsen thinks the mother probably contracted an asymptomatic infection from her husband, who recalled having a rash when she was 4 months pregnant. When they participated in a research study, both parents tested positive for Zika antibodies.
“The child had the classic symptoms of congenital Zika syndrome,” Dr. Nielsen said. “He was 9 months old, he had microcephaly, and he was having mal seizures.”
Researchers have since learned that children with such classic symptoms represent only a small proportion of those affected by prenatal Zika exposure – about 3%-5%. The virus was at its height during the 2016-2016 epidemic and is not currently causing outbreaks. But as researchers have followed cohorts of children exposed to Zika in utero, they have found many subtler effects physicians will need to monitor as the children grow up.
“When we’re seeing hundreds of kids with microcephaly, we had a lot of people infected,” Dr. Nielsen said. “Microcephaly is only the tip of the iceberg.”
Early evidence
Microcephaly may be the most identifiable symptom of fetal Zika infection, but researchers tracking cohorts of exposed children have begun to build a more complete picture of what long-term effects might look like. But hundreds, if not thousands, of children have been exposed to Zika in the womb – it’s not clear how many, Dr. Nielsen said – and many show a range of effects that don’t officially qualify as congenital Zika syndrome.
Current estimates suggest about one third of exposed children have some type of neurologic or neurodevelopmental problem, even though prevalence of visible effects is much lower. Over time, the incidence of these effects has fluctuated; some developmental delays and sensory deficits began manifesting later in childhood whereas others, at least in a few children, have resolved.
“We’re just beginning to have some of the data that we need to think about the full spectrum of outcomes,” said Cindy Moore, MD, chief medical officer in the Division of Congenital and Developmental Disorders in the Centers for Disease Control and Prevention’s National Center on Birth Defects and Developmental Disabilities.
“As we’re learning more and more, we’re learning the spectrum is expanding to less severe forms,” Dr. Moore said. “We do know that with some infections, there are later onset of problems.”
Studies published in 2018 described cohorts of children whose mothers had confirmed or suspected Zika infections during pregnancy in the French Territories of America (Guadalupe, Martinique, and French Guiana) and in Salvador, Brazil. The research provided valuable early data on the incidence of microcephaly and other severe effects in newborns, but noted the need for long-term follow up.
The U.S. Zika Pregnancy and Infant Registry is one of the largest such cohorts. In August 2018, researchers made their first report on data from the registry They looked at 1450 children age 1 or older who had undergone neuroimaging or screenings (developmental, vision, hearing) or both. In 6%, at least one birth defect was linked to Zika, and 9% had at least one neurodevelopmental abnormality.
As these children age past developmental milestones, more effects will likely manifest – even in those children whose appearance and imaging presented as healthy at birth.
Longer-term follow up
Nielsen at UCLA and M. Elisabeth Lopes Moreira, MD, of the Oswaldo Cruz Foundation in Rio de Janeiro, are following a cohort of more than 100 children born in Rio de Janeiro during Brazil’s 2015-2016 epidemic to mothers with symptomatic, PCR-confirmed Zika infections during pregnancy. In December 2018, their team reported that rates of severe neurodevelopmental delay and sensory dysfunction – 14% of 131 children aged 12-18 months – were higher than those found in earlier studies.
In August 2019, the team described neurodevelopmental, vision, and hearing outcomes in 216 Zika-exposed children 2 years after birth. They used the Bayley-III Scales of Infant and Toddler Development to assess cognitive, language and motor skills in 146 of the children. Forty percent of them were below or very below average in development, more than one third (35%) had language delays, 12% percent had hearing loss, and 7% had abnormal eye anatomy, such as underdeveloped retinas.
In two of the eight children in the cohort with microcephaly, the abnormality unexpectedly resolved. Although that finding received a lot of press, Dr. Nielsen pointed out that “not all microcephalies are created equal.”
In one case, a child born small for gestational age had proportional microcephaly: the baby›s head circumference met the criteria for microcephaly, but the infant›s head was proportional to the body so, as the child grew, the apparent microcephaly disappeared.
In the other case, the child was born with craniosynostosis, in which the skull sutures fuse too early – another effect seen with prenatal Zika exposure, Dr. Nielsen said. After corrective surgery, the child’s head circumference no longer met the definition of microcephaly, but the child still had symptoms related to congenital Zika: a developmental delay and calcifications in the brain. Meanwhile, two other children in the Rio cohort developed secondary microcephaly.
In another follow-up study of children up to age 4, Dr. Nielsen and colleagues found that both clinicians and family may think that Zika-exposed infants without microcephaly are developing normally, but that may not be true. Nearly 70% of children without microcephaly had neurologic abnormalities on physical examination, and more than half had failure to thrive because of poor feeding related to neurologic abnormalities.
Initially, some children may be able to mask subtle problems. A study published in January from Sarah B. Mulkey, MD, PhD, of Children’s National Hospital in Washington, DC, and colleagues described neurodevelopmental outcomes in 70 Colombian children up to 18 months old who had been exposed to Zika in utero. The children had a normal head circumference at birth and a normal fetal MRI, but – compared with typically developing peers – their communication, social cognition, and mobility scores on standardized assessments tended to decline as they got older.
“Especially in a very young child, there’s always going to be a possibility that you can compensate for a deficit, and it appears that at least some of these children are doing so,” said William J. Muller, MD, PhD, associate professor of pediatrics at Northwestern University, Chicago. When the children are older, certain behavioral effects will become easier to assess.
“With these children now approaching school age, understanding the full spectrum of neurodevelopmental abnormalities has important public health and educational system implications,” Dr. Muller and Dr. Mulkey wrote in a commentary about one of Dr. Nielsen’s studies.
Researchers face multiple barriers to understanding the long-term effects of fetal Zika infection. Many infants known to have been exposed in utero never received the recommended early assessments and haven’t been followed long-term. Particularly in Brazil, poverty, poor access to healthcare, and overcrowding all complicate surveillance efforts, Dr. Muller said. Stigma related to children’s neurodevelopmental problems also can potentially reduce a mother’s willingness to attend all follow-ups and assessments.
Some children may have been exposed but were never recognized as such, making it difficult for researchers to track their development and assemble a complete picture of prenatal Zika infection outcomes. Asymptomatic infection occurs in about 80% of Zika infections, though it’s not clear if that number holds for infections during pregnancy as well, according to Dr. Muller and Dr. Mulkey. Because nearly all the current research involves children whose mothers had symptomatic infections, the studies’ generalizability may be limited.
Those likely asymptomatic infections are also a major reason none of the cohorts have comparison groups.
“There are literally hundreds of things that can contribute to or cause developmental problems,” said Dr. Moore of the CDC, who noted that it would be nice to have a comparison group so as to know what Zika may not be responsible for. That said, it would be difficult-to-impossible to create a control group with similar geographic and demographic characteristics as the exposed children, a group who researchers can be certain weren’t exposed.
Neurodevelopmental disabilities occur in about 15% of the general population, making it difficult to determine whether Zika causes any or all long-term, less severe developmental findings in exposed children. The difficulty only compounds with time: the older a child is when a developmental problem is recognized, the harder it is to go back and say the problem is a result of something that occurred before birth, Dr. Moore said. “It’s a challenging field to say, this is what caused that outcome.”
Exposed children need continued evaluation
Interpreting the clinical implications of available studies is also challenging. It can be difficult to distinguish between central nervous system damage and peripheral damage, leaving the true etiology of poor vision or hearing elusive. The Zika virus can attack both the optic nerve and the part of the brain that interprets what a person sees: “Are you not seeing well because that part of your brain is not developed, or is it just a problem with the eye?” Dr. Nielsen said.
When problems can’t be precisely identified, successful interventions are harder. If the cochlea is normal, for instance, but the part of the brain that interprets sound or language has deficits, a hearing aid won’t help.
The services and interventions that children need depend on their specific developmental or cognitive deficits, regardless of the cause. But if clinicians know the cause is likely Zika exposure, they also know to look for other deficits.
Children showing likely effects of congenital Zika infection should be further evaluated for other possible birth defects and referred to a developmental specialist, early intervention services, and family support services. Depending on the child, primary care providers might consider referrals to an infectious disease specialist, clinical geneticist, neurologist, or other specialists.
Even with no confirmed infection or visible signs at birth, clinicians should remain vigilant with children who had possible exposure. A recently published study of 120 children conceived during the Zika outbreak in Paraíba, Brazil, assessed as infants and then again at 2 years old, exemplifies why. Researchers identified adverse neurologic outcomes and developmental delays in several children who had no physical evidence of birth defects as newborns, but whose antibody tests showed possible infection.
“In this post-epidemic period, with decreased Zika transmission and less public awareness,” wrote Dr. Mulkey and a colleague, “follow-up of these children is now more important than ever”.
A version of this article originally appeared on Medscape.com.
In 2020, “the virus” has come to mean one thing: SARS-CoV-2. But just a few years ago, Zika had the world's attention, as one news report after another described children with microcephaly born to women who'd been infected while pregnant.
It can be difficult for physicians to determine whether a birth defect is the result of Zika. Most infections have few or no symptoms, and mothers may not know if they’ve been exposed. Karin Nielsen, MD, remembers one child in particular, a 9-month-old boy born with microcephaly whose parents brought the infant to her in 2018 because he had started having seizures.
The child was born in Mexico in 2017, when the Zika virus was still known to be circulating in the Americas, said Dr. Nielsen, a pediatric infectious disease specialist at the University of California, Los Angeles. Brain imaging revealed calcifications and other signs in the boy’s brain that were consistent with exposure. But his mother said she was never sick during pregnancy.
Because Zika is transmitted not just via mosquito and from mother to fetus but also sexually, Dr. Nielsen thinks the mother probably contracted an asymptomatic infection from her husband, who recalled having a rash when she was 4 months pregnant. When they participated in a research study, both parents tested positive for Zika antibodies.
“The child had the classic symptoms of congenital Zika syndrome,” Dr. Nielsen said. “He was 9 months old, he had microcephaly, and he was having mal seizures.”
Researchers have since learned that children with such classic symptoms represent only a small proportion of those affected by prenatal Zika exposure – about 3%-5%. The virus was at its height during the 2016-2016 epidemic and is not currently causing outbreaks. But as researchers have followed cohorts of children exposed to Zika in utero, they have found many subtler effects physicians will need to monitor as the children grow up.
“When we’re seeing hundreds of kids with microcephaly, we had a lot of people infected,” Dr. Nielsen said. “Microcephaly is only the tip of the iceberg.”
Early evidence
Microcephaly may be the most identifiable symptom of fetal Zika infection, but researchers tracking cohorts of exposed children have begun to build a more complete picture of what long-term effects might look like. But hundreds, if not thousands, of children have been exposed to Zika in the womb – it’s not clear how many, Dr. Nielsen said – and many show a range of effects that don’t officially qualify as congenital Zika syndrome.
Current estimates suggest about one third of exposed children have some type of neurologic or neurodevelopmental problem, even though prevalence of visible effects is much lower. Over time, the incidence of these effects has fluctuated; some developmental delays and sensory deficits began manifesting later in childhood whereas others, at least in a few children, have resolved.
“We’re just beginning to have some of the data that we need to think about the full spectrum of outcomes,” said Cindy Moore, MD, chief medical officer in the Division of Congenital and Developmental Disorders in the Centers for Disease Control and Prevention’s National Center on Birth Defects and Developmental Disabilities.
“As we’re learning more and more, we’re learning the spectrum is expanding to less severe forms,” Dr. Moore said. “We do know that with some infections, there are later onset of problems.”
Studies published in 2018 described cohorts of children whose mothers had confirmed or suspected Zika infections during pregnancy in the French Territories of America (Guadalupe, Martinique, and French Guiana) and in Salvador, Brazil. The research provided valuable early data on the incidence of microcephaly and other severe effects in newborns, but noted the need for long-term follow up.
The U.S. Zika Pregnancy and Infant Registry is one of the largest such cohorts. In August 2018, researchers made their first report on data from the registry They looked at 1450 children age 1 or older who had undergone neuroimaging or screenings (developmental, vision, hearing) or both. In 6%, at least one birth defect was linked to Zika, and 9% had at least one neurodevelopmental abnormality.
As these children age past developmental milestones, more effects will likely manifest – even in those children whose appearance and imaging presented as healthy at birth.
Longer-term follow up
Nielsen at UCLA and M. Elisabeth Lopes Moreira, MD, of the Oswaldo Cruz Foundation in Rio de Janeiro, are following a cohort of more than 100 children born in Rio de Janeiro during Brazil’s 2015-2016 epidemic to mothers with symptomatic, PCR-confirmed Zika infections during pregnancy. In December 2018, their team reported that rates of severe neurodevelopmental delay and sensory dysfunction – 14% of 131 children aged 12-18 months – were higher than those found in earlier studies.
In August 2019, the team described neurodevelopmental, vision, and hearing outcomes in 216 Zika-exposed children 2 years after birth. They used the Bayley-III Scales of Infant and Toddler Development to assess cognitive, language and motor skills in 146 of the children. Forty percent of them were below or very below average in development, more than one third (35%) had language delays, 12% percent had hearing loss, and 7% had abnormal eye anatomy, such as underdeveloped retinas.
In two of the eight children in the cohort with microcephaly, the abnormality unexpectedly resolved. Although that finding received a lot of press, Dr. Nielsen pointed out that “not all microcephalies are created equal.”
In one case, a child born small for gestational age had proportional microcephaly: the baby›s head circumference met the criteria for microcephaly, but the infant›s head was proportional to the body so, as the child grew, the apparent microcephaly disappeared.
In the other case, the child was born with craniosynostosis, in which the skull sutures fuse too early – another effect seen with prenatal Zika exposure, Dr. Nielsen said. After corrective surgery, the child’s head circumference no longer met the definition of microcephaly, but the child still had symptoms related to congenital Zika: a developmental delay and calcifications in the brain. Meanwhile, two other children in the Rio cohort developed secondary microcephaly.
In another follow-up study of children up to age 4, Dr. Nielsen and colleagues found that both clinicians and family may think that Zika-exposed infants without microcephaly are developing normally, but that may not be true. Nearly 70% of children without microcephaly had neurologic abnormalities on physical examination, and more than half had failure to thrive because of poor feeding related to neurologic abnormalities.
Initially, some children may be able to mask subtle problems. A study published in January from Sarah B. Mulkey, MD, PhD, of Children’s National Hospital in Washington, DC, and colleagues described neurodevelopmental outcomes in 70 Colombian children up to 18 months old who had been exposed to Zika in utero. The children had a normal head circumference at birth and a normal fetal MRI, but – compared with typically developing peers – their communication, social cognition, and mobility scores on standardized assessments tended to decline as they got older.
“Especially in a very young child, there’s always going to be a possibility that you can compensate for a deficit, and it appears that at least some of these children are doing so,” said William J. Muller, MD, PhD, associate professor of pediatrics at Northwestern University, Chicago. When the children are older, certain behavioral effects will become easier to assess.
“With these children now approaching school age, understanding the full spectrum of neurodevelopmental abnormalities has important public health and educational system implications,” Dr. Muller and Dr. Mulkey wrote in a commentary about one of Dr. Nielsen’s studies.
Researchers face multiple barriers to understanding the long-term effects of fetal Zika infection. Many infants known to have been exposed in utero never received the recommended early assessments and haven’t been followed long-term. Particularly in Brazil, poverty, poor access to healthcare, and overcrowding all complicate surveillance efforts, Dr. Muller said. Stigma related to children’s neurodevelopmental problems also can potentially reduce a mother’s willingness to attend all follow-ups and assessments.
Some children may have been exposed but were never recognized as such, making it difficult for researchers to track their development and assemble a complete picture of prenatal Zika infection outcomes. Asymptomatic infection occurs in about 80% of Zika infections, though it’s not clear if that number holds for infections during pregnancy as well, according to Dr. Muller and Dr. Mulkey. Because nearly all the current research involves children whose mothers had symptomatic infections, the studies’ generalizability may be limited.
Those likely asymptomatic infections are also a major reason none of the cohorts have comparison groups.
“There are literally hundreds of things that can contribute to or cause developmental problems,” said Dr. Moore of the CDC, who noted that it would be nice to have a comparison group so as to know what Zika may not be responsible for. That said, it would be difficult-to-impossible to create a control group with similar geographic and demographic characteristics as the exposed children, a group who researchers can be certain weren’t exposed.
Neurodevelopmental disabilities occur in about 15% of the general population, making it difficult to determine whether Zika causes any or all long-term, less severe developmental findings in exposed children. The difficulty only compounds with time: the older a child is when a developmental problem is recognized, the harder it is to go back and say the problem is a result of something that occurred before birth, Dr. Moore said. “It’s a challenging field to say, this is what caused that outcome.”
Exposed children need continued evaluation
Interpreting the clinical implications of available studies is also challenging. It can be difficult to distinguish between central nervous system damage and peripheral damage, leaving the true etiology of poor vision or hearing elusive. The Zika virus can attack both the optic nerve and the part of the brain that interprets what a person sees: “Are you not seeing well because that part of your brain is not developed, or is it just a problem with the eye?” Dr. Nielsen said.
When problems can’t be precisely identified, successful interventions are harder. If the cochlea is normal, for instance, but the part of the brain that interprets sound or language has deficits, a hearing aid won’t help.
The services and interventions that children need depend on their specific developmental or cognitive deficits, regardless of the cause. But if clinicians know the cause is likely Zika exposure, they also know to look for other deficits.
Children showing likely effects of congenital Zika infection should be further evaluated for other possible birth defects and referred to a developmental specialist, early intervention services, and family support services. Depending on the child, primary care providers might consider referrals to an infectious disease specialist, clinical geneticist, neurologist, or other specialists.
Even with no confirmed infection or visible signs at birth, clinicians should remain vigilant with children who had possible exposure. A recently published study of 120 children conceived during the Zika outbreak in Paraíba, Brazil, assessed as infants and then again at 2 years old, exemplifies why. Researchers identified adverse neurologic outcomes and developmental delays in several children who had no physical evidence of birth defects as newborns, but whose antibody tests showed possible infection.
“In this post-epidemic period, with decreased Zika transmission and less public awareness,” wrote Dr. Mulkey and a colleague, “follow-up of these children is now more important than ever”.
A version of this article originally appeared on Medscape.com.
In 2020, “the virus” has come to mean one thing: SARS-CoV-2. But just a few years ago, Zika had the world's attention, as one news report after another described children with microcephaly born to women who'd been infected while pregnant.
It can be difficult for physicians to determine whether a birth defect is the result of Zika. Most infections have few or no symptoms, and mothers may not know if they’ve been exposed. Karin Nielsen, MD, remembers one child in particular, a 9-month-old boy born with microcephaly whose parents brought the infant to her in 2018 because he had started having seizures.
The child was born in Mexico in 2017, when the Zika virus was still known to be circulating in the Americas, said Dr. Nielsen, a pediatric infectious disease specialist at the University of California, Los Angeles. Brain imaging revealed calcifications and other signs in the boy’s brain that were consistent with exposure. But his mother said she was never sick during pregnancy.
Because Zika is transmitted not just via mosquito and from mother to fetus but also sexually, Dr. Nielsen thinks the mother probably contracted an asymptomatic infection from her husband, who recalled having a rash when she was 4 months pregnant. When they participated in a research study, both parents tested positive for Zika antibodies.
“The child had the classic symptoms of congenital Zika syndrome,” Dr. Nielsen said. “He was 9 months old, he had microcephaly, and he was having mal seizures.”
Researchers have since learned that children with such classic symptoms represent only a small proportion of those affected by prenatal Zika exposure – about 3%-5%. The virus was at its height during the 2016-2016 epidemic and is not currently causing outbreaks. But as researchers have followed cohorts of children exposed to Zika in utero, they have found many subtler effects physicians will need to monitor as the children grow up.
“When we’re seeing hundreds of kids with microcephaly, we had a lot of people infected,” Dr. Nielsen said. “Microcephaly is only the tip of the iceberg.”
Early evidence
Microcephaly may be the most identifiable symptom of fetal Zika infection, but researchers tracking cohorts of exposed children have begun to build a more complete picture of what long-term effects might look like. But hundreds, if not thousands, of children have been exposed to Zika in the womb – it’s not clear how many, Dr. Nielsen said – and many show a range of effects that don’t officially qualify as congenital Zika syndrome.
Current estimates suggest about one third of exposed children have some type of neurologic or neurodevelopmental problem, even though prevalence of visible effects is much lower. Over time, the incidence of these effects has fluctuated; some developmental delays and sensory deficits began manifesting later in childhood whereas others, at least in a few children, have resolved.
“We’re just beginning to have some of the data that we need to think about the full spectrum of outcomes,” said Cindy Moore, MD, chief medical officer in the Division of Congenital and Developmental Disorders in the Centers for Disease Control and Prevention’s National Center on Birth Defects and Developmental Disabilities.
“As we’re learning more and more, we’re learning the spectrum is expanding to less severe forms,” Dr. Moore said. “We do know that with some infections, there are later onset of problems.”
Studies published in 2018 described cohorts of children whose mothers had confirmed or suspected Zika infections during pregnancy in the French Territories of America (Guadalupe, Martinique, and French Guiana) and in Salvador, Brazil. The research provided valuable early data on the incidence of microcephaly and other severe effects in newborns, but noted the need for long-term follow up.
The U.S. Zika Pregnancy and Infant Registry is one of the largest such cohorts. In August 2018, researchers made their first report on data from the registry They looked at 1450 children age 1 or older who had undergone neuroimaging or screenings (developmental, vision, hearing) or both. In 6%, at least one birth defect was linked to Zika, and 9% had at least one neurodevelopmental abnormality.
As these children age past developmental milestones, more effects will likely manifest – even in those children whose appearance and imaging presented as healthy at birth.
Longer-term follow up
Nielsen at UCLA and M. Elisabeth Lopes Moreira, MD, of the Oswaldo Cruz Foundation in Rio de Janeiro, are following a cohort of more than 100 children born in Rio de Janeiro during Brazil’s 2015-2016 epidemic to mothers with symptomatic, PCR-confirmed Zika infections during pregnancy. In December 2018, their team reported that rates of severe neurodevelopmental delay and sensory dysfunction – 14% of 131 children aged 12-18 months – were higher than those found in earlier studies.
In August 2019, the team described neurodevelopmental, vision, and hearing outcomes in 216 Zika-exposed children 2 years after birth. They used the Bayley-III Scales of Infant and Toddler Development to assess cognitive, language and motor skills in 146 of the children. Forty percent of them were below or very below average in development, more than one third (35%) had language delays, 12% percent had hearing loss, and 7% had abnormal eye anatomy, such as underdeveloped retinas.
In two of the eight children in the cohort with microcephaly, the abnormality unexpectedly resolved. Although that finding received a lot of press, Dr. Nielsen pointed out that “not all microcephalies are created equal.”
In one case, a child born small for gestational age had proportional microcephaly: the baby›s head circumference met the criteria for microcephaly, but the infant›s head was proportional to the body so, as the child grew, the apparent microcephaly disappeared.
In the other case, the child was born with craniosynostosis, in which the skull sutures fuse too early – another effect seen with prenatal Zika exposure, Dr. Nielsen said. After corrective surgery, the child’s head circumference no longer met the definition of microcephaly, but the child still had symptoms related to congenital Zika: a developmental delay and calcifications in the brain. Meanwhile, two other children in the Rio cohort developed secondary microcephaly.
In another follow-up study of children up to age 4, Dr. Nielsen and colleagues found that both clinicians and family may think that Zika-exposed infants without microcephaly are developing normally, but that may not be true. Nearly 70% of children without microcephaly had neurologic abnormalities on physical examination, and more than half had failure to thrive because of poor feeding related to neurologic abnormalities.
Initially, some children may be able to mask subtle problems. A study published in January from Sarah B. Mulkey, MD, PhD, of Children’s National Hospital in Washington, DC, and colleagues described neurodevelopmental outcomes in 70 Colombian children up to 18 months old who had been exposed to Zika in utero. The children had a normal head circumference at birth and a normal fetal MRI, but – compared with typically developing peers – their communication, social cognition, and mobility scores on standardized assessments tended to decline as they got older.
“Especially in a very young child, there’s always going to be a possibility that you can compensate for a deficit, and it appears that at least some of these children are doing so,” said William J. Muller, MD, PhD, associate professor of pediatrics at Northwestern University, Chicago. When the children are older, certain behavioral effects will become easier to assess.
“With these children now approaching school age, understanding the full spectrum of neurodevelopmental abnormalities has important public health and educational system implications,” Dr. Muller and Dr. Mulkey wrote in a commentary about one of Dr. Nielsen’s studies.
Researchers face multiple barriers to understanding the long-term effects of fetal Zika infection. Many infants known to have been exposed in utero never received the recommended early assessments and haven’t been followed long-term. Particularly in Brazil, poverty, poor access to healthcare, and overcrowding all complicate surveillance efforts, Dr. Muller said. Stigma related to children’s neurodevelopmental problems also can potentially reduce a mother’s willingness to attend all follow-ups and assessments.
Some children may have been exposed but were never recognized as such, making it difficult for researchers to track their development and assemble a complete picture of prenatal Zika infection outcomes. Asymptomatic infection occurs in about 80% of Zika infections, though it’s not clear if that number holds for infections during pregnancy as well, according to Dr. Muller and Dr. Mulkey. Because nearly all the current research involves children whose mothers had symptomatic infections, the studies’ generalizability may be limited.
Those likely asymptomatic infections are also a major reason none of the cohorts have comparison groups.
“There are literally hundreds of things that can contribute to or cause developmental problems,” said Dr. Moore of the CDC, who noted that it would be nice to have a comparison group so as to know what Zika may not be responsible for. That said, it would be difficult-to-impossible to create a control group with similar geographic and demographic characteristics as the exposed children, a group who researchers can be certain weren’t exposed.
Neurodevelopmental disabilities occur in about 15% of the general population, making it difficult to determine whether Zika causes any or all long-term, less severe developmental findings in exposed children. The difficulty only compounds with time: the older a child is when a developmental problem is recognized, the harder it is to go back and say the problem is a result of something that occurred before birth, Dr. Moore said. “It’s a challenging field to say, this is what caused that outcome.”
Exposed children need continued evaluation
Interpreting the clinical implications of available studies is also challenging. It can be difficult to distinguish between central nervous system damage and peripheral damage, leaving the true etiology of poor vision or hearing elusive. The Zika virus can attack both the optic nerve and the part of the brain that interprets what a person sees: “Are you not seeing well because that part of your brain is not developed, or is it just a problem with the eye?” Dr. Nielsen said.
When problems can’t be precisely identified, successful interventions are harder. If the cochlea is normal, for instance, but the part of the brain that interprets sound or language has deficits, a hearing aid won’t help.
The services and interventions that children need depend on their specific developmental or cognitive deficits, regardless of the cause. But if clinicians know the cause is likely Zika exposure, they also know to look for other deficits.
Children showing likely effects of congenital Zika infection should be further evaluated for other possible birth defects and referred to a developmental specialist, early intervention services, and family support services. Depending on the child, primary care providers might consider referrals to an infectious disease specialist, clinical geneticist, neurologist, or other specialists.
Even with no confirmed infection or visible signs at birth, clinicians should remain vigilant with children who had possible exposure. A recently published study of 120 children conceived during the Zika outbreak in Paraíba, Brazil, assessed as infants and then again at 2 years old, exemplifies why. Researchers identified adverse neurologic outcomes and developmental delays in several children who had no physical evidence of birth defects as newborns, but whose antibody tests showed possible infection.
“In this post-epidemic period, with decreased Zika transmission and less public awareness,” wrote Dr. Mulkey and a colleague, “follow-up of these children is now more important than ever”.
A version of this article originally appeared on Medscape.com.
Melanoma experts say ‘no’ to routine gene profile testing
“The currently published evidence is insufficient to establish that routine use of GEP testing provides additional clinical value for melanoma staging and prognostication beyond available clinicopathologic variables,” they argued.
Patients must be protected “from potentially inaccurate testing that may provide a false sense of security or perceived increased risk” that could lead to the wrong decisions, they said in a consensus statement from the United States’ national Melanoma Prevention Working Group. The statement was published on July 29 in JAMA Dermatology.
The GEP test for melanoma that is available in the United States – DecisionDx-Melanoma from Castle Biosciences – checks the expression levels of 31 genes reported to be associated with melanoma metastasis and recurrence. It uses quantitative reverse transcriptase and polymerase chain reaction on RNA from formalin-fixed, paraffin-embedded biopsy specimens.
The test stratifies patients as being at low, intermediate, or high risk. It is marketed as a guide to whether to perform sentinel lymph node biopsies (SLNB) on patients age 55 years or older with tumors less than 2 mm deep and to decide what levels of follow-up, imaging, and adjuvant treatment are appropriate for tumors at least 0.3 mm deep.
Medicare reimburses at $7,193 per test for SLNB-eligible patients.
However, this test is not endorsed by the American Academy of Dermatology or National Comprehensive Cancer Network outside of studies because the evidence of benefit is not strong enough, the consensus authors noted.
Even so, use of the test is growing, with up to 10% of cutaneous melanomas now being tested in the United States.
Company welcomes “further discussions”
“To date, thousands of clinicians – over 4,200 US clinicians in the last 12 months – have utilized our GEP test for cutaneous melanoma in their patients after reviewing our clinical data and determining that our test provides clinically actionable information that complements current melanoma staging,” said Castle Biosciences Vice President of Research and Development Bob Cook, PhD, when asked for comment.
Citing company-funded studies, he said that “the strength of the existing evidence in support of these claims has undergone rigorous evaluation to obtain Medicare reimbursement.”
“We believe that the application of the test to help guide [the] decision to pursue SLNB has the potential to realize significant cost savings by reducing unnecessary SLNB procedures, particularly in the T1 population.”
Asked for a reaction to the consensus statement, Dr. Cook said in an interview: “We recently launched two prospective studies with multiple centers nationwide that will involve thousands of patients and provide additional data relating our tests to patient outcomes. ... We welcome further discussions to promote collaborative efforts with centers that are part of the [Melanoma Prevention Working Group] to improve patient outcomes.”
Cart before the horse
Medicare, although it reimburses the test, has its doubts. Due to the “low strength of evidence,” the Centers for Medicare & Medicaid Services said in their local coverage determination that continued reimbursement depends on demonstration of 95% or greater distant-metastasis–free survival and melanoma-specific survival at 3 years “in patients directed to no SLNB by the test compared to standard of care, and ... evidence of higher SLNB positivity in patients selected for this procedure by the test compared to standard of care.”
The statement hints at the Achilles’ heel of GEP in melanoma – that is, the lack of evidence that test results improve outcomes. This was the main concern of the consensus statement; the cart is before the horse.
One of the consensus authors, David Polsky, MD, PhD, professor of dermatologic oncology at New York University, New York City, said that “most of the data for this test come from retrospectively collected patient groups.” The prospective studies have been generally small, with no comparator group. “While they have shown some promise in intermediate thickness melanoma, they have not yet demonstrated utility for thin, stage I melanomas.”
First, do no harm
A new meta-analysis of over 800 patients with cutaneous melanoma tested by DecisionDx-Melanoma, published in JAMA Dermatology alongside the consensus statement, shows how the tests perform.
Among patients with a recurrence, DecisionDx-Melanoma correctly classified 82% with stage II disease but only 29% with stage I disease as high risk. Among those without recurrence, the test correctly classified 90% of stage I patients but only 44% with stage II disease as low risk.
Similar results were seen with the melanoma GEP test available in Europe, MelaGenix (NeraCare GmbH). This test was developed from a panel that was narrowed to seven protective genes and one high-risk gene using a training cohort of 125 cutaneous melanomas.
“The prognostic ability of GEP tests ... appeared to be poor at correctly identifying recurrence in patients with stage I disease, suggesting limited potential for clinical utility in these patients,” commented the meta-analysis authors, led by Michael Marchetti, MD, an assistant professor of dermatology at Weill Cornell Medical College in New York City.
“Unknown are the harms associated with a false-positive result, which were 10-fold more frequent than true-positive results in patients with stage I disease,” they pointed out.
“Further research is needed to define the incremental improvement in risk predictions provided by the test beyond ... all other known clinicopathologic factors,” which include patient sex, age, tumor location and thickness, ulceration, mitotic rate, lymphovascular invasion, microsatellites, and other factors proven to be linked to outcomes, they said.
Studies so far suggesting benefit have incorporated a few of those factors, but not all of them. For now, “it is not clear which patients should be tested or how to act on the results,” Dr. Marchetti and colleagues concluded.
Breast cancer standard of proof
Larger, prospective studies are needed to address whether GEP testing can replace SLNB to predict relapse “and [can identify] patients who could be spared surveillance imaging and/or benefit from adjuvant therapy,” wrote the consensus authors. Follow-up also needs to be long enough to detect delayed recurrence of thin melanomas, they added.
With more research, there is reason to hope that gene expression profiling will help in melanoma; it’s already standard of care in breast cancer, they pointed out.
On the hope front, one cohort study evaluated whether DecisionDx-Melanoma could identify patients at low risk for positive lymph nodes in T1/T2 disease who were eligible for biopsy. Only 1.6% of subjects who were aged 65 years or older and identified by the test as low risk had a positive node.
“This is a promising direction of investigation ... in a narrow, defined population,” noted authors led by Carrie Kovarik, MD, associate professor of dermatology at the University of Pennsylvania, Philadelphia, in an opinion piece last spring.
But still, until there’s “clear evidence that [DecisionDx-Melanoma] results affect patient outcomes, we should not use it to influence care decisions in patients with thin” melanomas. Dermatology “should expect the same standards” of proof as breast cancer, they wrote.
What to do right now?
Despite the marketing, “think twice before ordering GEP tests for” T1a melanomas is the message in an editorial that accompanies the consensus statement. The 5- and 10-year melanoma-specific survival rates are 99% and 98%, respectively. GEP tests are unlikely to change these estimates significantly. In fact, the new meta-analysis indicates “that there may be an approximately 12% misassignment rate in this population,” wrote editorialists Warren Chan, of Baylor College of Medicine, Houston and Hensin Tsao, MD, PhD, director of the melanoma genetics program at Massachusetts General Hospital, Boston.
“Even if you use GEP testing and discover a low-risk class assignment for a 2 mm thick melanoma, avoid the urge to bypass the sentinel lymph node discussion. ... Nodal sampling, for good reasons, remains part of all major guidelines and determines eligibility for adjuvant treatments. ... Many of us engaged in genomics research believe that accurate [melanoma] GEP will be developed in time, but better tools and greater tenacity are needed,” they wrote.
There was no industry funding for the consensus statement and meta-analysis. Authors on the consensus statement reported numerous ties to pharmaceutical and other companies, as listed in the paper.
A version of this article originally appeared on Medscape.com.
“The currently published evidence is insufficient to establish that routine use of GEP testing provides additional clinical value for melanoma staging and prognostication beyond available clinicopathologic variables,” they argued.
Patients must be protected “from potentially inaccurate testing that may provide a false sense of security or perceived increased risk” that could lead to the wrong decisions, they said in a consensus statement from the United States’ national Melanoma Prevention Working Group. The statement was published on July 29 in JAMA Dermatology.
The GEP test for melanoma that is available in the United States – DecisionDx-Melanoma from Castle Biosciences – checks the expression levels of 31 genes reported to be associated with melanoma metastasis and recurrence. It uses quantitative reverse transcriptase and polymerase chain reaction on RNA from formalin-fixed, paraffin-embedded biopsy specimens.
The test stratifies patients as being at low, intermediate, or high risk. It is marketed as a guide to whether to perform sentinel lymph node biopsies (SLNB) on patients age 55 years or older with tumors less than 2 mm deep and to decide what levels of follow-up, imaging, and adjuvant treatment are appropriate for tumors at least 0.3 mm deep.
Medicare reimburses at $7,193 per test for SLNB-eligible patients.
However, this test is not endorsed by the American Academy of Dermatology or National Comprehensive Cancer Network outside of studies because the evidence of benefit is not strong enough, the consensus authors noted.
Even so, use of the test is growing, with up to 10% of cutaneous melanomas now being tested in the United States.
Company welcomes “further discussions”
“To date, thousands of clinicians – over 4,200 US clinicians in the last 12 months – have utilized our GEP test for cutaneous melanoma in their patients after reviewing our clinical data and determining that our test provides clinically actionable information that complements current melanoma staging,” said Castle Biosciences Vice President of Research and Development Bob Cook, PhD, when asked for comment.
Citing company-funded studies, he said that “the strength of the existing evidence in support of these claims has undergone rigorous evaluation to obtain Medicare reimbursement.”
“We believe that the application of the test to help guide [the] decision to pursue SLNB has the potential to realize significant cost savings by reducing unnecessary SLNB procedures, particularly in the T1 population.”
Asked for a reaction to the consensus statement, Dr. Cook said in an interview: “We recently launched two prospective studies with multiple centers nationwide that will involve thousands of patients and provide additional data relating our tests to patient outcomes. ... We welcome further discussions to promote collaborative efforts with centers that are part of the [Melanoma Prevention Working Group] to improve patient outcomes.”
Cart before the horse
Medicare, although it reimburses the test, has its doubts. Due to the “low strength of evidence,” the Centers for Medicare & Medicaid Services said in their local coverage determination that continued reimbursement depends on demonstration of 95% or greater distant-metastasis–free survival and melanoma-specific survival at 3 years “in patients directed to no SLNB by the test compared to standard of care, and ... evidence of higher SLNB positivity in patients selected for this procedure by the test compared to standard of care.”
The statement hints at the Achilles’ heel of GEP in melanoma – that is, the lack of evidence that test results improve outcomes. This was the main concern of the consensus statement; the cart is before the horse.
One of the consensus authors, David Polsky, MD, PhD, professor of dermatologic oncology at New York University, New York City, said that “most of the data for this test come from retrospectively collected patient groups.” The prospective studies have been generally small, with no comparator group. “While they have shown some promise in intermediate thickness melanoma, they have not yet demonstrated utility for thin, stage I melanomas.”
First, do no harm
A new meta-analysis of over 800 patients with cutaneous melanoma tested by DecisionDx-Melanoma, published in JAMA Dermatology alongside the consensus statement, shows how the tests perform.
Among patients with a recurrence, DecisionDx-Melanoma correctly classified 82% with stage II disease but only 29% with stage I disease as high risk. Among those without recurrence, the test correctly classified 90% of stage I patients but only 44% with stage II disease as low risk.
Similar results were seen with the melanoma GEP test available in Europe, MelaGenix (NeraCare GmbH). This test was developed from a panel that was narrowed to seven protective genes and one high-risk gene using a training cohort of 125 cutaneous melanomas.
“The prognostic ability of GEP tests ... appeared to be poor at correctly identifying recurrence in patients with stage I disease, suggesting limited potential for clinical utility in these patients,” commented the meta-analysis authors, led by Michael Marchetti, MD, an assistant professor of dermatology at Weill Cornell Medical College in New York City.
“Unknown are the harms associated with a false-positive result, which were 10-fold more frequent than true-positive results in patients with stage I disease,” they pointed out.
“Further research is needed to define the incremental improvement in risk predictions provided by the test beyond ... all other known clinicopathologic factors,” which include patient sex, age, tumor location and thickness, ulceration, mitotic rate, lymphovascular invasion, microsatellites, and other factors proven to be linked to outcomes, they said.
Studies so far suggesting benefit have incorporated a few of those factors, but not all of them. For now, “it is not clear which patients should be tested or how to act on the results,” Dr. Marchetti and colleagues concluded.
Breast cancer standard of proof
Larger, prospective studies are needed to address whether GEP testing can replace SLNB to predict relapse “and [can identify] patients who could be spared surveillance imaging and/or benefit from adjuvant therapy,” wrote the consensus authors. Follow-up also needs to be long enough to detect delayed recurrence of thin melanomas, they added.
With more research, there is reason to hope that gene expression profiling will help in melanoma; it’s already standard of care in breast cancer, they pointed out.
On the hope front, one cohort study evaluated whether DecisionDx-Melanoma could identify patients at low risk for positive lymph nodes in T1/T2 disease who were eligible for biopsy. Only 1.6% of subjects who were aged 65 years or older and identified by the test as low risk had a positive node.
“This is a promising direction of investigation ... in a narrow, defined population,” noted authors led by Carrie Kovarik, MD, associate professor of dermatology at the University of Pennsylvania, Philadelphia, in an opinion piece last spring.
But still, until there’s “clear evidence that [DecisionDx-Melanoma] results affect patient outcomes, we should not use it to influence care decisions in patients with thin” melanomas. Dermatology “should expect the same standards” of proof as breast cancer, they wrote.
What to do right now?
Despite the marketing, “think twice before ordering GEP tests for” T1a melanomas is the message in an editorial that accompanies the consensus statement. The 5- and 10-year melanoma-specific survival rates are 99% and 98%, respectively. GEP tests are unlikely to change these estimates significantly. In fact, the new meta-analysis indicates “that there may be an approximately 12% misassignment rate in this population,” wrote editorialists Warren Chan, of Baylor College of Medicine, Houston and Hensin Tsao, MD, PhD, director of the melanoma genetics program at Massachusetts General Hospital, Boston.
“Even if you use GEP testing and discover a low-risk class assignment for a 2 mm thick melanoma, avoid the urge to bypass the sentinel lymph node discussion. ... Nodal sampling, for good reasons, remains part of all major guidelines and determines eligibility for adjuvant treatments. ... Many of us engaged in genomics research believe that accurate [melanoma] GEP will be developed in time, but better tools and greater tenacity are needed,” they wrote.
There was no industry funding for the consensus statement and meta-analysis. Authors on the consensus statement reported numerous ties to pharmaceutical and other companies, as listed in the paper.
A version of this article originally appeared on Medscape.com.
“The currently published evidence is insufficient to establish that routine use of GEP testing provides additional clinical value for melanoma staging and prognostication beyond available clinicopathologic variables,” they argued.
Patients must be protected “from potentially inaccurate testing that may provide a false sense of security or perceived increased risk” that could lead to the wrong decisions, they said in a consensus statement from the United States’ national Melanoma Prevention Working Group. The statement was published on July 29 in JAMA Dermatology.
The GEP test for melanoma that is available in the United States – DecisionDx-Melanoma from Castle Biosciences – checks the expression levels of 31 genes reported to be associated with melanoma metastasis and recurrence. It uses quantitative reverse transcriptase and polymerase chain reaction on RNA from formalin-fixed, paraffin-embedded biopsy specimens.
The test stratifies patients as being at low, intermediate, or high risk. It is marketed as a guide to whether to perform sentinel lymph node biopsies (SLNB) on patients age 55 years or older with tumors less than 2 mm deep and to decide what levels of follow-up, imaging, and adjuvant treatment are appropriate for tumors at least 0.3 mm deep.
Medicare reimburses at $7,193 per test for SLNB-eligible patients.
However, this test is not endorsed by the American Academy of Dermatology or National Comprehensive Cancer Network outside of studies because the evidence of benefit is not strong enough, the consensus authors noted.
Even so, use of the test is growing, with up to 10% of cutaneous melanomas now being tested in the United States.
Company welcomes “further discussions”
“To date, thousands of clinicians – over 4,200 US clinicians in the last 12 months – have utilized our GEP test for cutaneous melanoma in their patients after reviewing our clinical data and determining that our test provides clinically actionable information that complements current melanoma staging,” said Castle Biosciences Vice President of Research and Development Bob Cook, PhD, when asked for comment.
Citing company-funded studies, he said that “the strength of the existing evidence in support of these claims has undergone rigorous evaluation to obtain Medicare reimbursement.”
“We believe that the application of the test to help guide [the] decision to pursue SLNB has the potential to realize significant cost savings by reducing unnecessary SLNB procedures, particularly in the T1 population.”
Asked for a reaction to the consensus statement, Dr. Cook said in an interview: “We recently launched two prospective studies with multiple centers nationwide that will involve thousands of patients and provide additional data relating our tests to patient outcomes. ... We welcome further discussions to promote collaborative efforts with centers that are part of the [Melanoma Prevention Working Group] to improve patient outcomes.”
Cart before the horse
Medicare, although it reimburses the test, has its doubts. Due to the “low strength of evidence,” the Centers for Medicare & Medicaid Services said in their local coverage determination that continued reimbursement depends on demonstration of 95% or greater distant-metastasis–free survival and melanoma-specific survival at 3 years “in patients directed to no SLNB by the test compared to standard of care, and ... evidence of higher SLNB positivity in patients selected for this procedure by the test compared to standard of care.”
The statement hints at the Achilles’ heel of GEP in melanoma – that is, the lack of evidence that test results improve outcomes. This was the main concern of the consensus statement; the cart is before the horse.
One of the consensus authors, David Polsky, MD, PhD, professor of dermatologic oncology at New York University, New York City, said that “most of the data for this test come from retrospectively collected patient groups.” The prospective studies have been generally small, with no comparator group. “While they have shown some promise in intermediate thickness melanoma, they have not yet demonstrated utility for thin, stage I melanomas.”
First, do no harm
A new meta-analysis of over 800 patients with cutaneous melanoma tested by DecisionDx-Melanoma, published in JAMA Dermatology alongside the consensus statement, shows how the tests perform.
Among patients with a recurrence, DecisionDx-Melanoma correctly classified 82% with stage II disease but only 29% with stage I disease as high risk. Among those without recurrence, the test correctly classified 90% of stage I patients but only 44% with stage II disease as low risk.
Similar results were seen with the melanoma GEP test available in Europe, MelaGenix (NeraCare GmbH). This test was developed from a panel that was narrowed to seven protective genes and one high-risk gene using a training cohort of 125 cutaneous melanomas.
“The prognostic ability of GEP tests ... appeared to be poor at correctly identifying recurrence in patients with stage I disease, suggesting limited potential for clinical utility in these patients,” commented the meta-analysis authors, led by Michael Marchetti, MD, an assistant professor of dermatology at Weill Cornell Medical College in New York City.
“Unknown are the harms associated with a false-positive result, which were 10-fold more frequent than true-positive results in patients with stage I disease,” they pointed out.
“Further research is needed to define the incremental improvement in risk predictions provided by the test beyond ... all other known clinicopathologic factors,” which include patient sex, age, tumor location and thickness, ulceration, mitotic rate, lymphovascular invasion, microsatellites, and other factors proven to be linked to outcomes, they said.
Studies so far suggesting benefit have incorporated a few of those factors, but not all of them. For now, “it is not clear which patients should be tested or how to act on the results,” Dr. Marchetti and colleagues concluded.
Breast cancer standard of proof
Larger, prospective studies are needed to address whether GEP testing can replace SLNB to predict relapse “and [can identify] patients who could be spared surveillance imaging and/or benefit from adjuvant therapy,” wrote the consensus authors. Follow-up also needs to be long enough to detect delayed recurrence of thin melanomas, they added.
With more research, there is reason to hope that gene expression profiling will help in melanoma; it’s already standard of care in breast cancer, they pointed out.
On the hope front, one cohort study evaluated whether DecisionDx-Melanoma could identify patients at low risk for positive lymph nodes in T1/T2 disease who were eligible for biopsy. Only 1.6% of subjects who were aged 65 years or older and identified by the test as low risk had a positive node.
“This is a promising direction of investigation ... in a narrow, defined population,” noted authors led by Carrie Kovarik, MD, associate professor of dermatology at the University of Pennsylvania, Philadelphia, in an opinion piece last spring.
But still, until there’s “clear evidence that [DecisionDx-Melanoma] results affect patient outcomes, we should not use it to influence care decisions in patients with thin” melanomas. Dermatology “should expect the same standards” of proof as breast cancer, they wrote.
What to do right now?
Despite the marketing, “think twice before ordering GEP tests for” T1a melanomas is the message in an editorial that accompanies the consensus statement. The 5- and 10-year melanoma-specific survival rates are 99% and 98%, respectively. GEP tests are unlikely to change these estimates significantly. In fact, the new meta-analysis indicates “that there may be an approximately 12% misassignment rate in this population,” wrote editorialists Warren Chan, of Baylor College of Medicine, Houston and Hensin Tsao, MD, PhD, director of the melanoma genetics program at Massachusetts General Hospital, Boston.
“Even if you use GEP testing and discover a low-risk class assignment for a 2 mm thick melanoma, avoid the urge to bypass the sentinel lymph node discussion. ... Nodal sampling, for good reasons, remains part of all major guidelines and determines eligibility for adjuvant treatments. ... Many of us engaged in genomics research believe that accurate [melanoma] GEP will be developed in time, but better tools and greater tenacity are needed,” they wrote.
There was no industry funding for the consensus statement and meta-analysis. Authors on the consensus statement reported numerous ties to pharmaceutical and other companies, as listed in the paper.
A version of this article originally appeared on Medscape.com.
There is no cure for gullibility
Metformin, oleander extract, azithromycin, famotidine, fluvoxamine, hydroxychloroquine, indomethacin, remdesivir, different vaccines, and many others. What does this disparate group of agents have in common? They’re all being bandied about as treatments for COVID-19.
This sort of thing makes big headlines in the news when someone even mentions them as a possible treatment, but so do proposed treatments for Alzheimer’s disease, various cancers, and other devastating illnesses. It triggers calls to doctors’ offices by patients wanting to be put on them, demands for them to be sold over the counter, and less-then-scrupulous people selling all kinds of things claiming to contain them and cure the disease for only $89.95 with free shipping if you act now.
Even in ordinary times (whatever that means anymore) it doesn’t take much for even a hint of success to make the news, spiking calls to doctors’ offices asking about “that new treatment I saw.” Of course, the number of drugs that are proven to be successful and come to market is a fraction of what’s actually tested.
Since the many failures don’t make headlines like successes do, the general public moves on and doesn’t even remember the initial story after a while. Only the medical and pharmaceutical professions are left to remember “we tried that, it didn’t work.”
We learn as much from failure as we do from success – sometimes more – but failure doesn’t make headlines or sell papers or get clicks.
The research scientists and physicians know this and how long it can take to find something that works. In some diseases it still hasn’t happened, in spite of billions spent and decades going by.
Unfortunately, nonscientific people (which is most of the population) just see our remarkable breakthroughs evidenced by shiny equipment and new drugs, and only read the headlines about successes. They don’t realize the many years and failures behind them.
It doesn’t help to have nonmedical talking heads on the news egging this belief on. The few voices of reason are drowned out.
The polio virus was identified in 1908 (the disease is thousands of years old). The Salk vaccine came out in 1955. That’s a 47-year gap. I doubt it will take that long for COVID-19, but the point is that these things never have, and never will, happen overnight.
The problem isn’t science or medicine. It’s unreasonable expectations for immediate success. While science and diseases may change over time, human nature doesn’t.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Metformin, oleander extract, azithromycin, famotidine, fluvoxamine, hydroxychloroquine, indomethacin, remdesivir, different vaccines, and many others. What does this disparate group of agents have in common? They’re all being bandied about as treatments for COVID-19.
This sort of thing makes big headlines in the news when someone even mentions them as a possible treatment, but so do proposed treatments for Alzheimer’s disease, various cancers, and other devastating illnesses. It triggers calls to doctors’ offices by patients wanting to be put on them, demands for them to be sold over the counter, and less-then-scrupulous people selling all kinds of things claiming to contain them and cure the disease for only $89.95 with free shipping if you act now.
Even in ordinary times (whatever that means anymore) it doesn’t take much for even a hint of success to make the news, spiking calls to doctors’ offices asking about “that new treatment I saw.” Of course, the number of drugs that are proven to be successful and come to market is a fraction of what’s actually tested.
Since the many failures don’t make headlines like successes do, the general public moves on and doesn’t even remember the initial story after a while. Only the medical and pharmaceutical professions are left to remember “we tried that, it didn’t work.”
We learn as much from failure as we do from success – sometimes more – but failure doesn’t make headlines or sell papers or get clicks.
The research scientists and physicians know this and how long it can take to find something that works. In some diseases it still hasn’t happened, in spite of billions spent and decades going by.
Unfortunately, nonscientific people (which is most of the population) just see our remarkable breakthroughs evidenced by shiny equipment and new drugs, and only read the headlines about successes. They don’t realize the many years and failures behind them.
It doesn’t help to have nonmedical talking heads on the news egging this belief on. The few voices of reason are drowned out.
The polio virus was identified in 1908 (the disease is thousands of years old). The Salk vaccine came out in 1955. That’s a 47-year gap. I doubt it will take that long for COVID-19, but the point is that these things never have, and never will, happen overnight.
The problem isn’t science or medicine. It’s unreasonable expectations for immediate success. While science and diseases may change over time, human nature doesn’t.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Metformin, oleander extract, azithromycin, famotidine, fluvoxamine, hydroxychloroquine, indomethacin, remdesivir, different vaccines, and many others. What does this disparate group of agents have in common? They’re all being bandied about as treatments for COVID-19.
This sort of thing makes big headlines in the news when someone even mentions them as a possible treatment, but so do proposed treatments for Alzheimer’s disease, various cancers, and other devastating illnesses. It triggers calls to doctors’ offices by patients wanting to be put on them, demands for them to be sold over the counter, and less-then-scrupulous people selling all kinds of things claiming to contain them and cure the disease for only $89.95 with free shipping if you act now.
Even in ordinary times (whatever that means anymore) it doesn’t take much for even a hint of success to make the news, spiking calls to doctors’ offices asking about “that new treatment I saw.” Of course, the number of drugs that are proven to be successful and come to market is a fraction of what’s actually tested.
Since the many failures don’t make headlines like successes do, the general public moves on and doesn’t even remember the initial story after a while. Only the medical and pharmaceutical professions are left to remember “we tried that, it didn’t work.”
We learn as much from failure as we do from success – sometimes more – but failure doesn’t make headlines or sell papers or get clicks.
The research scientists and physicians know this and how long it can take to find something that works. In some diseases it still hasn’t happened, in spite of billions spent and decades going by.
Unfortunately, nonscientific people (which is most of the population) just see our remarkable breakthroughs evidenced by shiny equipment and new drugs, and only read the headlines about successes. They don’t realize the many years and failures behind them.
It doesn’t help to have nonmedical talking heads on the news egging this belief on. The few voices of reason are drowned out.
The polio virus was identified in 1908 (the disease is thousands of years old). The Salk vaccine came out in 1955. That’s a 47-year gap. I doubt it will take that long for COVID-19, but the point is that these things never have, and never will, happen overnight.
The problem isn’t science or medicine. It’s unreasonable expectations for immediate success. While science and diseases may change over time, human nature doesn’t.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Evolocumab safe and effective in pediatric FH
The PCSK9 monoclonal antibody evolocumab (Repatha) was well tolerated and effectively lowered LDL cholesterol by 38% compared with placebo in a randomized controlled trial in pediatric patients with heterozygous familial hypercholesterolemia (FH) already taking statins with or without ezetimibe.
“HAUSER-RCT is the largest study and the first placebo-controlled randomized trial of a PCSK9 inhibitor in pediatric FH,” senior author Daniel Gaudet, MD, PhD, Universite de Montreal, said in an interview.
“The study showed good safety and efficacy of the drug in this population, with an excellent 44% reduction in LDL cholesterol compared with 6% in the placebo group.”
The trial also found evolocumab to be well tolerated in this group, with adverse effects similar in the active and placebo groups.
“Some people have wondered about using a drug with a monthly injection in a pediatric population, but this was not an issue in our study,” Dr. Gaudet said. “The idea of a monthly injection was well received, and no patient withdrew because of this.”
The HAUSER-RCT trial was presented on Aug. 29 at the virtual annual congress of the European Society of Cardiology (ESC Congress 2020) and simultaneously published online in the New England Journal of Medicine.
“With patients recruited from 23 countries in five continents, the study provides an accurate picture of the safety and efficacy of evolocumab in pediatric FH patients worldwide,” Dr. Gaudet said.
The 24-week, randomized, double-blind, placebo-controlled trial involved 157 patients aged 10-17 years with heterozygous FH already taking statins with or without ezetimibe and who had an LDL cholesterol level of 130 mg/dL or more and a triglyceride level of 400 mg/dL or less.
They were randomly assigned in a 2:1 ratio to receive monthly subcutaneous injections of evolocumab (420 mg) or placebo.
Results showed that at week 24, the mean percentage change from baseline in LDL cholesterol level was −44.5% in the evolocumab group and −6.2% in the placebo group, giving a difference of −38.3 percentage points (P < .001).
The absolute change in the LDL cholesterol level was −77.5 mg/dL in the evolocumab group and −9.0 mg/dL in the placebo group, giving a difference of −68.6 mg/dL (P < .001).
Results for all secondary lipid variables were significantly better with evolocumab than with placebo. The incidence of adverse events that occurred during the treatment period was similar in the evolocumab and placebo groups. Laboratory abnormalities did not differ between groups.
Dr. Gaudet noted that FH is the most common genetic disease worldwide, affecting 1 in 250 people. “It is very treatable, so it is important to identify these patients, but it is massively underdiagnosed, with only around 15%-20% of patients with the condition having been identified,” he said.
“The vast majority of pediatric FH patients can reach target LDL levels with statins and ezetimibe, but there are 5%-10% of patients who may need additional therapy. We have now shown that evolocumab is safe and effective for these patients and can be used to fill this gap,” Dr. Gaudet said. “We can now say that we can cover all situations in treating FH whatever the severity of the disease.”
However, the challenge remains to improve the diagnosis of FH. “If there is one person with FH in a family, then it is essential that the whole extended family is tested. Our toolbox for treating this condition is now sufficiently effective, so there is no reason not to diagnose this disease,” Dr. Gaudet stressed.
The HAUSER-RCT study was supported by Amgen. Gaudet reports grants and personal fees from Amgen during the conduct of the study.
A version of this article originally appeared on Medscape.com.
The PCSK9 monoclonal antibody evolocumab (Repatha) was well tolerated and effectively lowered LDL cholesterol by 38% compared with placebo in a randomized controlled trial in pediatric patients with heterozygous familial hypercholesterolemia (FH) already taking statins with or without ezetimibe.
“HAUSER-RCT is the largest study and the first placebo-controlled randomized trial of a PCSK9 inhibitor in pediatric FH,” senior author Daniel Gaudet, MD, PhD, Universite de Montreal, said in an interview.
“The study showed good safety and efficacy of the drug in this population, with an excellent 44% reduction in LDL cholesterol compared with 6% in the placebo group.”
The trial also found evolocumab to be well tolerated in this group, with adverse effects similar in the active and placebo groups.
“Some people have wondered about using a drug with a monthly injection in a pediatric population, but this was not an issue in our study,” Dr. Gaudet said. “The idea of a monthly injection was well received, and no patient withdrew because of this.”
The HAUSER-RCT trial was presented on Aug. 29 at the virtual annual congress of the European Society of Cardiology (ESC Congress 2020) and simultaneously published online in the New England Journal of Medicine.
“With patients recruited from 23 countries in five continents, the study provides an accurate picture of the safety and efficacy of evolocumab in pediatric FH patients worldwide,” Dr. Gaudet said.
The 24-week, randomized, double-blind, placebo-controlled trial involved 157 patients aged 10-17 years with heterozygous FH already taking statins with or without ezetimibe and who had an LDL cholesterol level of 130 mg/dL or more and a triglyceride level of 400 mg/dL or less.
They were randomly assigned in a 2:1 ratio to receive monthly subcutaneous injections of evolocumab (420 mg) or placebo.
Results showed that at week 24, the mean percentage change from baseline in LDL cholesterol level was −44.5% in the evolocumab group and −6.2% in the placebo group, giving a difference of −38.3 percentage points (P < .001).
The absolute change in the LDL cholesterol level was −77.5 mg/dL in the evolocumab group and −9.0 mg/dL in the placebo group, giving a difference of −68.6 mg/dL (P < .001).
Results for all secondary lipid variables were significantly better with evolocumab than with placebo. The incidence of adverse events that occurred during the treatment period was similar in the evolocumab and placebo groups. Laboratory abnormalities did not differ between groups.
Dr. Gaudet noted that FH is the most common genetic disease worldwide, affecting 1 in 250 people. “It is very treatable, so it is important to identify these patients, but it is massively underdiagnosed, with only around 15%-20% of patients with the condition having been identified,” he said.
“The vast majority of pediatric FH patients can reach target LDL levels with statins and ezetimibe, but there are 5%-10% of patients who may need additional therapy. We have now shown that evolocumab is safe and effective for these patients and can be used to fill this gap,” Dr. Gaudet said. “We can now say that we can cover all situations in treating FH whatever the severity of the disease.”
However, the challenge remains to improve the diagnosis of FH. “If there is one person with FH in a family, then it is essential that the whole extended family is tested. Our toolbox for treating this condition is now sufficiently effective, so there is no reason not to diagnose this disease,” Dr. Gaudet stressed.
The HAUSER-RCT study was supported by Amgen. Gaudet reports grants and personal fees from Amgen during the conduct of the study.
A version of this article originally appeared on Medscape.com.
The PCSK9 monoclonal antibody evolocumab (Repatha) was well tolerated and effectively lowered LDL cholesterol by 38% compared with placebo in a randomized controlled trial in pediatric patients with heterozygous familial hypercholesterolemia (FH) already taking statins with or without ezetimibe.
“HAUSER-RCT is the largest study and the first placebo-controlled randomized trial of a PCSK9 inhibitor in pediatric FH,” senior author Daniel Gaudet, MD, PhD, Universite de Montreal, said in an interview.
“The study showed good safety and efficacy of the drug in this population, with an excellent 44% reduction in LDL cholesterol compared with 6% in the placebo group.”
The trial also found evolocumab to be well tolerated in this group, with adverse effects similar in the active and placebo groups.
“Some people have wondered about using a drug with a monthly injection in a pediatric population, but this was not an issue in our study,” Dr. Gaudet said. “The idea of a monthly injection was well received, and no patient withdrew because of this.”
The HAUSER-RCT trial was presented on Aug. 29 at the virtual annual congress of the European Society of Cardiology (ESC Congress 2020) and simultaneously published online in the New England Journal of Medicine.
“With patients recruited from 23 countries in five continents, the study provides an accurate picture of the safety and efficacy of evolocumab in pediatric FH patients worldwide,” Dr. Gaudet said.
The 24-week, randomized, double-blind, placebo-controlled trial involved 157 patients aged 10-17 years with heterozygous FH already taking statins with or without ezetimibe and who had an LDL cholesterol level of 130 mg/dL or more and a triglyceride level of 400 mg/dL or less.
They were randomly assigned in a 2:1 ratio to receive monthly subcutaneous injections of evolocumab (420 mg) or placebo.
Results showed that at week 24, the mean percentage change from baseline in LDL cholesterol level was −44.5% in the evolocumab group and −6.2% in the placebo group, giving a difference of −38.3 percentage points (P < .001).
The absolute change in the LDL cholesterol level was −77.5 mg/dL in the evolocumab group and −9.0 mg/dL in the placebo group, giving a difference of −68.6 mg/dL (P < .001).
Results for all secondary lipid variables were significantly better with evolocumab than with placebo. The incidence of adverse events that occurred during the treatment period was similar in the evolocumab and placebo groups. Laboratory abnormalities did not differ between groups.
Dr. Gaudet noted that FH is the most common genetic disease worldwide, affecting 1 in 250 people. “It is very treatable, so it is important to identify these patients, but it is massively underdiagnosed, with only around 15%-20% of patients with the condition having been identified,” he said.
“The vast majority of pediatric FH patients can reach target LDL levels with statins and ezetimibe, but there are 5%-10% of patients who may need additional therapy. We have now shown that evolocumab is safe and effective for these patients and can be used to fill this gap,” Dr. Gaudet said. “We can now say that we can cover all situations in treating FH whatever the severity of the disease.”
However, the challenge remains to improve the diagnosis of FH. “If there is one person with FH in a family, then it is essential that the whole extended family is tested. Our toolbox for treating this condition is now sufficiently effective, so there is no reason not to diagnose this disease,” Dr. Gaudet stressed.
The HAUSER-RCT study was supported by Amgen. Gaudet reports grants and personal fees from Amgen during the conduct of the study.
A version of this article originally appeared on Medscape.com.
Black diabetics lose limbs at triple the rate of others. Here’s how health care leaders are starting to act.
Prompted by a ProPublica story that detailed how Black Americans with diabetes lose limbs at a rate triple that of others, the American Diabetes Association has included an initiative to prevent unnecessary amputations as part of an unprecedented campaign to reduce racial disparities in diabetes care.
“The ProPublica article raised the consciousness of what the problem is,” said Tracey Brown, the CEO of the ADA. “Every four minutes, someone is losing a limb from diabetic complications. That’s ridiculous. We have got to find a way to drive change.”
The story highlighted obstacles to equitable care for diabetic patients at risk of amputation, from the government’s decision not to endorse screening at-risk patients for vascular disease in the legs, to the inadequate incentives for certain specialists to move to underserved areas, to the health system’s failure to consider limb-saving options before permitting surgeons to apply a blade.
In the weeks that followed publication, several congressional and state legislative offices reached out to the association to ask for guidance on drafting policy to reduce disparities in diabetic amputations. In response, the organization decided to build an agenda around the issue.
The ADA’s Health Equity Now campaign, which addresses the cost of diabetes care, nutrition, discrimination, and more, was motivated by the racial health disparities that have been exposed by COVID-19, which has hit Black Americans with diabetes particularly hard. As part of the project, the association has built a Health Equity Bill of Rights, asserting that all diabetes patients are entitled to affordable drugs, healthy food, the latest medical advances, and other protections.
The right to avoid preventable amputations is the only complication of uncontrolled diabetes that is included in the list. The organization is sharing the document with policymakers, practitioners, and patients as it begins to look toward policy change. It is also encouraging members of the public to ask their governors to support the project.
Dr. Ronald Dalman, president of the Society for Vascular Surgery, said: “I commend the ADA for doubling down on this particular complication of poorly managed diabetes. It’s a long overdue prioritization.” He added that it’s a “moment in time where we can leverage this concern about health care disparities to call out a very specific problem: the prevalence of amputation in certain subsets of the population.”
Dr. Gary Puckrein, head of the National Minority Quality Forum, a nonprofit focused on reducing health care disparities, said that the ADA’s efforts are just a step. “The American health care system was organized during an era when inequality was acceptable and mainstream in American society,” he said. “It’s not that African Americans are sicker, it’s that the health care delivered is unequal.”
He said he hopes that the national conversation on health disparities will mirror the conversation about police violence against Black Americans. “You, in effect, have your knees on their neck in the health care system as well when you don’t provide them with the care that they need.”
Two weeks after publication of the story, Rep. Bennie Thompson, a Democrat from Mississippi, honored Dr. Foluso Fakorede, the main subject of the ProPublica article, for his work in reducing unnecessary amputations in Bolivar County, Mississippi. The acknowledgment, made in the House of Representatives, referenced ProPublica’s findings.
The co-chairs of the Congressional Peripheral Artery Disease Caucus — Rep. Donald M. Payne Jr., a Democrat from New Jersey, and Rep. Gus Bilirakis, a Republican from Florida — have also begun work on a bill to address disparities in amputations, particularly for people with peripheral artery disease, a condition in which clogged arteries in the legs limit the flow of blood.
“The ProPublica article has brought strong awareness and real interest from a variety of parties — from the medical field and from patients and from potentially future patients,” said a spokesman for Payne. “We have been working with Bilirakis and other members to move this forward, with the ultimate goal of introducing legislation.”
Summer Blevins, deputy chief of staff for Bilirakis, added that their legislative ambition “is based on the basic principle that prevention, education and early intervention is best for the patient and also saves money.”
This story was originally published by ProPublica.
Prompted by a ProPublica story that detailed how Black Americans with diabetes lose limbs at a rate triple that of others, the American Diabetes Association has included an initiative to prevent unnecessary amputations as part of an unprecedented campaign to reduce racial disparities in diabetes care.
“The ProPublica article raised the consciousness of what the problem is,” said Tracey Brown, the CEO of the ADA. “Every four minutes, someone is losing a limb from diabetic complications. That’s ridiculous. We have got to find a way to drive change.”
The story highlighted obstacles to equitable care for diabetic patients at risk of amputation, from the government’s decision not to endorse screening at-risk patients for vascular disease in the legs, to the inadequate incentives for certain specialists to move to underserved areas, to the health system’s failure to consider limb-saving options before permitting surgeons to apply a blade.
In the weeks that followed publication, several congressional and state legislative offices reached out to the association to ask for guidance on drafting policy to reduce disparities in diabetic amputations. In response, the organization decided to build an agenda around the issue.
The ADA’s Health Equity Now campaign, which addresses the cost of diabetes care, nutrition, discrimination, and more, was motivated by the racial health disparities that have been exposed by COVID-19, which has hit Black Americans with diabetes particularly hard. As part of the project, the association has built a Health Equity Bill of Rights, asserting that all diabetes patients are entitled to affordable drugs, healthy food, the latest medical advances, and other protections.
The right to avoid preventable amputations is the only complication of uncontrolled diabetes that is included in the list. The organization is sharing the document with policymakers, practitioners, and patients as it begins to look toward policy change. It is also encouraging members of the public to ask their governors to support the project.
Dr. Ronald Dalman, president of the Society for Vascular Surgery, said: “I commend the ADA for doubling down on this particular complication of poorly managed diabetes. It’s a long overdue prioritization.” He added that it’s a “moment in time where we can leverage this concern about health care disparities to call out a very specific problem: the prevalence of amputation in certain subsets of the population.”
Dr. Gary Puckrein, head of the National Minority Quality Forum, a nonprofit focused on reducing health care disparities, said that the ADA’s efforts are just a step. “The American health care system was organized during an era when inequality was acceptable and mainstream in American society,” he said. “It’s not that African Americans are sicker, it’s that the health care delivered is unequal.”
He said he hopes that the national conversation on health disparities will mirror the conversation about police violence against Black Americans. “You, in effect, have your knees on their neck in the health care system as well when you don’t provide them with the care that they need.”
Two weeks after publication of the story, Rep. Bennie Thompson, a Democrat from Mississippi, honored Dr. Foluso Fakorede, the main subject of the ProPublica article, for his work in reducing unnecessary amputations in Bolivar County, Mississippi. The acknowledgment, made in the House of Representatives, referenced ProPublica’s findings.
The co-chairs of the Congressional Peripheral Artery Disease Caucus — Rep. Donald M. Payne Jr., a Democrat from New Jersey, and Rep. Gus Bilirakis, a Republican from Florida — have also begun work on a bill to address disparities in amputations, particularly for people with peripheral artery disease, a condition in which clogged arteries in the legs limit the flow of blood.
“The ProPublica article has brought strong awareness and real interest from a variety of parties — from the medical field and from patients and from potentially future patients,” said a spokesman for Payne. “We have been working with Bilirakis and other members to move this forward, with the ultimate goal of introducing legislation.”
Summer Blevins, deputy chief of staff for Bilirakis, added that their legislative ambition “is based on the basic principle that prevention, education and early intervention is best for the patient and also saves money.”
This story was originally published by ProPublica.
Prompted by a ProPublica story that detailed how Black Americans with diabetes lose limbs at a rate triple that of others, the American Diabetes Association has included an initiative to prevent unnecessary amputations as part of an unprecedented campaign to reduce racial disparities in diabetes care.
“The ProPublica article raised the consciousness of what the problem is,” said Tracey Brown, the CEO of the ADA. “Every four minutes, someone is losing a limb from diabetic complications. That’s ridiculous. We have got to find a way to drive change.”
The story highlighted obstacles to equitable care for diabetic patients at risk of amputation, from the government’s decision not to endorse screening at-risk patients for vascular disease in the legs, to the inadequate incentives for certain specialists to move to underserved areas, to the health system’s failure to consider limb-saving options before permitting surgeons to apply a blade.
In the weeks that followed publication, several congressional and state legislative offices reached out to the association to ask for guidance on drafting policy to reduce disparities in diabetic amputations. In response, the organization decided to build an agenda around the issue.
The ADA’s Health Equity Now campaign, which addresses the cost of diabetes care, nutrition, discrimination, and more, was motivated by the racial health disparities that have been exposed by COVID-19, which has hit Black Americans with diabetes particularly hard. As part of the project, the association has built a Health Equity Bill of Rights, asserting that all diabetes patients are entitled to affordable drugs, healthy food, the latest medical advances, and other protections.
The right to avoid preventable amputations is the only complication of uncontrolled diabetes that is included in the list. The organization is sharing the document with policymakers, practitioners, and patients as it begins to look toward policy change. It is also encouraging members of the public to ask their governors to support the project.
Dr. Ronald Dalman, president of the Society for Vascular Surgery, said: “I commend the ADA for doubling down on this particular complication of poorly managed diabetes. It’s a long overdue prioritization.” He added that it’s a “moment in time where we can leverage this concern about health care disparities to call out a very specific problem: the prevalence of amputation in certain subsets of the population.”
Dr. Gary Puckrein, head of the National Minority Quality Forum, a nonprofit focused on reducing health care disparities, said that the ADA’s efforts are just a step. “The American health care system was organized during an era when inequality was acceptable and mainstream in American society,” he said. “It’s not that African Americans are sicker, it’s that the health care delivered is unequal.”
He said he hopes that the national conversation on health disparities will mirror the conversation about police violence against Black Americans. “You, in effect, have your knees on their neck in the health care system as well when you don’t provide them with the care that they need.”
Two weeks after publication of the story, Rep. Bennie Thompson, a Democrat from Mississippi, honored Dr. Foluso Fakorede, the main subject of the ProPublica article, for his work in reducing unnecessary amputations in Bolivar County, Mississippi. The acknowledgment, made in the House of Representatives, referenced ProPublica’s findings.
The co-chairs of the Congressional Peripheral Artery Disease Caucus — Rep. Donald M. Payne Jr., a Democrat from New Jersey, and Rep. Gus Bilirakis, a Republican from Florida — have also begun work on a bill to address disparities in amputations, particularly for people with peripheral artery disease, a condition in which clogged arteries in the legs limit the flow of blood.
“The ProPublica article has brought strong awareness and real interest from a variety of parties — from the medical field and from patients and from potentially future patients,” said a spokesman for Payne. “We have been working with Bilirakis and other members to move this forward, with the ultimate goal of introducing legislation.”
Summer Blevins, deputy chief of staff for Bilirakis, added that their legislative ambition “is based on the basic principle that prevention, education and early intervention is best for the patient and also saves money.”
This story was originally published by ProPublica.
What is your diagnosis? - September 2020
Capillaria hepatica infection
The liver parenchyma shows spindle-shaped eosinophilic eggs surrounded by eosinophilic inflammatory infiltrates and epithelioid granuloma (original magnification ×200). Figure B shows spindle-shaped eosinophilic eggs with shells, radial striations, and visible polar body, containing granular eosinophilic debris (original magnification ×1000), consistent with Capillaria hepatica. Figure C reveals crescent-shaped, degenerated adult worms of C. hepatica showing longitudinal bacillary bands, vacuolated intestine, and convoluted gonads surrounded by intense eosinophilic inflammation in liver parenchyma (original magnification ×400). The outer cuticle is not appreciated because the worms are degenerated.
A review of history revealed that the child played with stray cats and had pica. He was given 10 mg/kg of oral albendazole for 16 weeks and 1 mg/kg of oral prednisolone for the first 2 weeks to prevent paradoxical inflammatory response. Thereafter, prednisolone was tapered and stopped. Pyrexia, liver size, AEC, and liver enzymes normalized at 24 hours, 72 hours, 4 months, and 5 months, respectively. At 12 months of follow-up, the child is asymptomatic.
Capillaria hepatica is a rare nematodal invasive parasitosis where humans are the dead-end host; the main lifecycle occurs between rodents and their predators. Adult worms live, mate, and lay noninfective unembryonated eggs in rodent livers. Embryogenesis occurs only after contact with the soil in two settings: 1) the rodent is eaten by the predator and the unembryonated eggs are released in the predator's feces or 2) carcass disintegration after natural death of the rodent. Humans incidentally ingest the infective embryonated eggs by soil to mouth transmission. They hatch in the human intestine and the larvae migrate through the portal vein into the liver where they mature into adult worms. In the liver, the cycle continues with the adult worms mating and laying eggs. This elicits intense inflammation with systemic symptoms.1 In the index case, we hypothesize that the toddler with pica would have come in contact with soil in the vicinity of the stray cats. This soil would have initially contained the feline feces with unembryonated eggs that later underwent embryogenesis. The triad of fever, hepatomegaly, and eosinophilia is the hallmark and characteristic liver histology clinches the diagnosis. Duration of anthelminthic therapy should be guided by AEC response.2,3
References
1. Wright K.A. Observation on the life cycle of Capillaria hepatica with a description of the adult. Can J Zool. 1961;39:167-82.
2. Berger T. Degrémont A. Gebbers J.O. et al. Hepatic capillariasis in a 1-year-old child. Eur J Pediatr. 1990;149:333-633.
3. Choe G. Lee H.S. Seo J.K. et al. Hepatic capillariasis: first case report in the Republic of Korea. Am J Trop Med Hyg. 1993;48:610-25.
Capillaria hepatica infection
The liver parenchyma shows spindle-shaped eosinophilic eggs surrounded by eosinophilic inflammatory infiltrates and epithelioid granuloma (original magnification ×200). Figure B shows spindle-shaped eosinophilic eggs with shells, radial striations, and visible polar body, containing granular eosinophilic debris (original magnification ×1000), consistent with Capillaria hepatica. Figure C reveals crescent-shaped, degenerated adult worms of C. hepatica showing longitudinal bacillary bands, vacuolated intestine, and convoluted gonads surrounded by intense eosinophilic inflammation in liver parenchyma (original magnification ×400). The outer cuticle is not appreciated because the worms are degenerated.
A review of history revealed that the child played with stray cats and had pica. He was given 10 mg/kg of oral albendazole for 16 weeks and 1 mg/kg of oral prednisolone for the first 2 weeks to prevent paradoxical inflammatory response. Thereafter, prednisolone was tapered and stopped. Pyrexia, liver size, AEC, and liver enzymes normalized at 24 hours, 72 hours, 4 months, and 5 months, respectively. At 12 months of follow-up, the child is asymptomatic.
Capillaria hepatica is a rare nematodal invasive parasitosis where humans are the dead-end host; the main lifecycle occurs between rodents and their predators. Adult worms live, mate, and lay noninfective unembryonated eggs in rodent livers. Embryogenesis occurs only after contact with the soil in two settings: 1) the rodent is eaten by the predator and the unembryonated eggs are released in the predator's feces or 2) carcass disintegration after natural death of the rodent. Humans incidentally ingest the infective embryonated eggs by soil to mouth transmission. They hatch in the human intestine and the larvae migrate through the portal vein into the liver where they mature into adult worms. In the liver, the cycle continues with the adult worms mating and laying eggs. This elicits intense inflammation with systemic symptoms.1 In the index case, we hypothesize that the toddler with pica would have come in contact with soil in the vicinity of the stray cats. This soil would have initially contained the feline feces with unembryonated eggs that later underwent embryogenesis. The triad of fever, hepatomegaly, and eosinophilia is the hallmark and characteristic liver histology clinches the diagnosis. Duration of anthelminthic therapy should be guided by AEC response.2,3
References
1. Wright K.A. Observation on the life cycle of Capillaria hepatica with a description of the adult. Can J Zool. 1961;39:167-82.
2. Berger T. Degrémont A. Gebbers J.O. et al. Hepatic capillariasis in a 1-year-old child. Eur J Pediatr. 1990;149:333-633.
3. Choe G. Lee H.S. Seo J.K. et al. Hepatic capillariasis: first case report in the Republic of Korea. Am J Trop Med Hyg. 1993;48:610-25.
Capillaria hepatica infection
The liver parenchyma shows spindle-shaped eosinophilic eggs surrounded by eosinophilic inflammatory infiltrates and epithelioid granuloma (original magnification ×200). Figure B shows spindle-shaped eosinophilic eggs with shells, radial striations, and visible polar body, containing granular eosinophilic debris (original magnification ×1000), consistent with Capillaria hepatica. Figure C reveals crescent-shaped, degenerated adult worms of C. hepatica showing longitudinal bacillary bands, vacuolated intestine, and convoluted gonads surrounded by intense eosinophilic inflammation in liver parenchyma (original magnification ×400). The outer cuticle is not appreciated because the worms are degenerated.
A review of history revealed that the child played with stray cats and had pica. He was given 10 mg/kg of oral albendazole for 16 weeks and 1 mg/kg of oral prednisolone for the first 2 weeks to prevent paradoxical inflammatory response. Thereafter, prednisolone was tapered and stopped. Pyrexia, liver size, AEC, and liver enzymes normalized at 24 hours, 72 hours, 4 months, and 5 months, respectively. At 12 months of follow-up, the child is asymptomatic.
Capillaria hepatica is a rare nematodal invasive parasitosis where humans are the dead-end host; the main lifecycle occurs between rodents and their predators. Adult worms live, mate, and lay noninfective unembryonated eggs in rodent livers. Embryogenesis occurs only after contact with the soil in two settings: 1) the rodent is eaten by the predator and the unembryonated eggs are released in the predator's feces or 2) carcass disintegration after natural death of the rodent. Humans incidentally ingest the infective embryonated eggs by soil to mouth transmission. They hatch in the human intestine and the larvae migrate through the portal vein into the liver where they mature into adult worms. In the liver, the cycle continues with the adult worms mating and laying eggs. This elicits intense inflammation with systemic symptoms.1 In the index case, we hypothesize that the toddler with pica would have come in contact with soil in the vicinity of the stray cats. This soil would have initially contained the feline feces with unembryonated eggs that later underwent embryogenesis. The triad of fever, hepatomegaly, and eosinophilia is the hallmark and characteristic liver histology clinches the diagnosis. Duration of anthelminthic therapy should be guided by AEC response.2,3
References
1. Wright K.A. Observation on the life cycle of Capillaria hepatica with a description of the adult. Can J Zool. 1961;39:167-82.
2. Berger T. Degrémont A. Gebbers J.O. et al. Hepatic capillariasis in a 1-year-old child. Eur J Pediatr. 1990;149:333-633.
3. Choe G. Lee H.S. Seo J.K. et al. Hepatic capillariasis: first case report in the Republic of Korea. Am J Trop Med Hyg. 1993;48:610-25.
A 15-month-old, previously thriving boy from western urban India was brought in with high-grade pyrexia of unknown origin for the last 45 days. He had received multiple courses of antibiotics and antimalarials elsewhere without any response. Appetite and general activity were preserved. Examination revealed mild pallor, significant nontender soft hepatomegaly (liver span of 14 cm) without splenomegaly or peripheral lymphadenopathy. Investigations showed a hemoglobin of 9 g/dL, microcytic hypochromic smear, total leukocyte count of 48,900/mm3, neutrophils at 16%, lymphocytes at 23%, eosinophils at 58%, absolute eosinophil count of 28,362/mm3, platelet count of 490,000/mm3, bilirubin of 0.8 mg/dL, aspartate aminotransferase of 203 IU/L, alanine aminotransferase of 179 IU/L, total protein of 9.3 g/dL, albumin of 3.6 g/dL, alkaline phosphatase of 203 IU/L, and gamma-glutamyl transpeptidase of 107 IU/L. Ultrasound examination and computed tomography scans of abdomen showed no focal lesions or abscesses. A bone marrow biopsy revealed an increase in eosinophils and its precursors. Echocardiography, retroviral serology, and multiple blood and urine cultures were unyielding. Liver biopsy was performed for diagnosis (Figures A-C).
Gut bacteria linked to cardiovascular, other health conditions
Microorganisms in the human digestive tract are linked to 29 specific health conditions, including chronic obstructive pulmonary disease, high blood pressure, and type 2 diabetes, according to a genome analysis in more than 400,000 individuals.
Although previous studies have suggested a link between gut microbiota and diseases in humans, “the extent to which the human gut microbiome can be considered a determinant of disease and healthy aging remains unknown,” Hilde E. Groot, MD, of the University of Groningen (The Netherlands), said in a presentation at the virtual annual congress of the European Society of Cardiology.
To identify the spectrum of diseases linked to the gut microbiome, the researchers identified 422,417 unrelated adults of White British ancestry with genotype and matching genetic data. The average age of the participants was 57 years and 46% were male.
The researchers conducted a phenomewide association study including 35 distinct single-nucleotide polymorphisms (SNPs) that are known to influence the microbiome of the human gut.
Overall, seven SNPs were significantly associated with 29 disease outcomes including hypertension, type 2 diabetes, hypercholesterolemia, heart failure, renal failure, and osteoarthritis.
In addition, after a further sensitivity analysis using a Mendelian randomization (MR) approach, associations between Ruminococcus flavefaciens and hypertension and between Clostridium and platelet count might point to a causal link, the researchers said.
“Over the past few years, the amount of research concerning the human gut microbiome and the associations with health and disease has tremendously increased. However, most studies investigated one or a few traits. The strength of our study is the possibility to cover a wide range of traits simultaneously within one population,” Dr. Groot said in an interview.
“Our data support the hypothesis that the human gut microbiome is a complex system, involved in many pathophysiological mechanisms in the human body. So, our results are additional to earlier research and strengthen this hypothesis,” Dr. Groot added.
“Microbiota and their metabolites might be of importance in the interplay between overlapping pathophysiological processes, and could serve as potential therapeutic targets for the maintenance of health and prevention and treatment of cardiovascular diseases. However, before it is possible to give advice for the public and medical practice, further research is needed to study causality,” she emphasized.
“Currently, it is too soon to advise patients concerning their microbiome,” Dr. Groot noted. “However, genetic studies like ours might help other researchers to study causality between the gut microbiome and particular traits, which might potentially lead to new therapeutic targets. Next to genetic variants as a proxy, we’re currently studying the gut microbiome composition in myocardial infarction patients and healthy controls in a longitudinal setting.”
“Previous studies have suggested a potential link between the gut microbiome and the development of cardiovascular disease, type 2 diabetes mellitus, and other chronic disorders,” Carol Ann Remme, MD, of the Amsterdam University Medical Center, said in an interview. “However, it is challenging to study the effect of gut microbiome composition in large patient cohorts. As an alternative approach, the study authors showed in a very large population that genetic variants previously shown to influence gut microbiome composition were significantly associated with conditions such as hypertension, type 2 diabetes, hypercholesterolemia, and heart failure.”
The study is unique in that it employed a very large cohort of more than 400,000 individuals, which is typically required to be able to draw clear conclusions, Dr. Remme continued. “The authors were able to further refine their findings by linking genetic variants known to influence specific gut bacteria to some particular disorders,” she noted.
“It is becoming increasingly clear that an individual’s gut microbiome composition, which is defined by both genetic and environmental factors such as diet, may affect his/her susceptibility to certain diseases – including cardiovascular – in addition to disease progression and outcome,” said Dr. Remme. “This may ultimately lead to development of novel, personalized strategies for risk stratification in addition to potential preventive measures targeting the gut microbiome. I expect this area of research will become increasingly important in the coming years.”
The study received no outside funding. Dr. Groot and colleagues had no financial conflicts to disclose. Dr. Remme had no financial conflicts to disclose.
Microorganisms in the human digestive tract are linked to 29 specific health conditions, including chronic obstructive pulmonary disease, high blood pressure, and type 2 diabetes, according to a genome analysis in more than 400,000 individuals.
Although previous studies have suggested a link between gut microbiota and diseases in humans, “the extent to which the human gut microbiome can be considered a determinant of disease and healthy aging remains unknown,” Hilde E. Groot, MD, of the University of Groningen (The Netherlands), said in a presentation at the virtual annual congress of the European Society of Cardiology.
To identify the spectrum of diseases linked to the gut microbiome, the researchers identified 422,417 unrelated adults of White British ancestry with genotype and matching genetic data. The average age of the participants was 57 years and 46% were male.
The researchers conducted a phenomewide association study including 35 distinct single-nucleotide polymorphisms (SNPs) that are known to influence the microbiome of the human gut.
Overall, seven SNPs were significantly associated with 29 disease outcomes including hypertension, type 2 diabetes, hypercholesterolemia, heart failure, renal failure, and osteoarthritis.
In addition, after a further sensitivity analysis using a Mendelian randomization (MR) approach, associations between Ruminococcus flavefaciens and hypertension and between Clostridium and platelet count might point to a causal link, the researchers said.
“Over the past few years, the amount of research concerning the human gut microbiome and the associations with health and disease has tremendously increased. However, most studies investigated one or a few traits. The strength of our study is the possibility to cover a wide range of traits simultaneously within one population,” Dr. Groot said in an interview.
“Our data support the hypothesis that the human gut microbiome is a complex system, involved in many pathophysiological mechanisms in the human body. So, our results are additional to earlier research and strengthen this hypothesis,” Dr. Groot added.
“Microbiota and their metabolites might be of importance in the interplay between overlapping pathophysiological processes, and could serve as potential therapeutic targets for the maintenance of health and prevention and treatment of cardiovascular diseases. However, before it is possible to give advice for the public and medical practice, further research is needed to study causality,” she emphasized.
“Currently, it is too soon to advise patients concerning their microbiome,” Dr. Groot noted. “However, genetic studies like ours might help other researchers to study causality between the gut microbiome and particular traits, which might potentially lead to new therapeutic targets. Next to genetic variants as a proxy, we’re currently studying the gut microbiome composition in myocardial infarction patients and healthy controls in a longitudinal setting.”
“Previous studies have suggested a potential link between the gut microbiome and the development of cardiovascular disease, type 2 diabetes mellitus, and other chronic disorders,” Carol Ann Remme, MD, of the Amsterdam University Medical Center, said in an interview. “However, it is challenging to study the effect of gut microbiome composition in large patient cohorts. As an alternative approach, the study authors showed in a very large population that genetic variants previously shown to influence gut microbiome composition were significantly associated with conditions such as hypertension, type 2 diabetes, hypercholesterolemia, and heart failure.”
The study is unique in that it employed a very large cohort of more than 400,000 individuals, which is typically required to be able to draw clear conclusions, Dr. Remme continued. “The authors were able to further refine their findings by linking genetic variants known to influence specific gut bacteria to some particular disorders,” she noted.
“It is becoming increasingly clear that an individual’s gut microbiome composition, which is defined by both genetic and environmental factors such as diet, may affect his/her susceptibility to certain diseases – including cardiovascular – in addition to disease progression and outcome,” said Dr. Remme. “This may ultimately lead to development of novel, personalized strategies for risk stratification in addition to potential preventive measures targeting the gut microbiome. I expect this area of research will become increasingly important in the coming years.”
The study received no outside funding. Dr. Groot and colleagues had no financial conflicts to disclose. Dr. Remme had no financial conflicts to disclose.
Microorganisms in the human digestive tract are linked to 29 specific health conditions, including chronic obstructive pulmonary disease, high blood pressure, and type 2 diabetes, according to a genome analysis in more than 400,000 individuals.
Although previous studies have suggested a link between gut microbiota and diseases in humans, “the extent to which the human gut microbiome can be considered a determinant of disease and healthy aging remains unknown,” Hilde E. Groot, MD, of the University of Groningen (The Netherlands), said in a presentation at the virtual annual congress of the European Society of Cardiology.
To identify the spectrum of diseases linked to the gut microbiome, the researchers identified 422,417 unrelated adults of White British ancestry with genotype and matching genetic data. The average age of the participants was 57 years and 46% were male.
The researchers conducted a phenomewide association study including 35 distinct single-nucleotide polymorphisms (SNPs) that are known to influence the microbiome of the human gut.
Overall, seven SNPs were significantly associated with 29 disease outcomes including hypertension, type 2 diabetes, hypercholesterolemia, heart failure, renal failure, and osteoarthritis.
In addition, after a further sensitivity analysis using a Mendelian randomization (MR) approach, associations between Ruminococcus flavefaciens and hypertension and between Clostridium and platelet count might point to a causal link, the researchers said.
“Over the past few years, the amount of research concerning the human gut microbiome and the associations with health and disease has tremendously increased. However, most studies investigated one or a few traits. The strength of our study is the possibility to cover a wide range of traits simultaneously within one population,” Dr. Groot said in an interview.
“Our data support the hypothesis that the human gut microbiome is a complex system, involved in many pathophysiological mechanisms in the human body. So, our results are additional to earlier research and strengthen this hypothesis,” Dr. Groot added.
“Microbiota and their metabolites might be of importance in the interplay between overlapping pathophysiological processes, and could serve as potential therapeutic targets for the maintenance of health and prevention and treatment of cardiovascular diseases. However, before it is possible to give advice for the public and medical practice, further research is needed to study causality,” she emphasized.
“Currently, it is too soon to advise patients concerning their microbiome,” Dr. Groot noted. “However, genetic studies like ours might help other researchers to study causality between the gut microbiome and particular traits, which might potentially lead to new therapeutic targets. Next to genetic variants as a proxy, we’re currently studying the gut microbiome composition in myocardial infarction patients and healthy controls in a longitudinal setting.”
“Previous studies have suggested a potential link between the gut microbiome and the development of cardiovascular disease, type 2 diabetes mellitus, and other chronic disorders,” Carol Ann Remme, MD, of the Amsterdam University Medical Center, said in an interview. “However, it is challenging to study the effect of gut microbiome composition in large patient cohorts. As an alternative approach, the study authors showed in a very large population that genetic variants previously shown to influence gut microbiome composition were significantly associated with conditions such as hypertension, type 2 diabetes, hypercholesterolemia, and heart failure.”
The study is unique in that it employed a very large cohort of more than 400,000 individuals, which is typically required to be able to draw clear conclusions, Dr. Remme continued. “The authors were able to further refine their findings by linking genetic variants known to influence specific gut bacteria to some particular disorders,” she noted.
“It is becoming increasingly clear that an individual’s gut microbiome composition, which is defined by both genetic and environmental factors such as diet, may affect his/her susceptibility to certain diseases – including cardiovascular – in addition to disease progression and outcome,” said Dr. Remme. “This may ultimately lead to development of novel, personalized strategies for risk stratification in addition to potential preventive measures targeting the gut microbiome. I expect this area of research will become increasingly important in the coming years.”
The study received no outside funding. Dr. Groot and colleagues had no financial conflicts to disclose. Dr. Remme had no financial conflicts to disclose.
FROM ESC CONGRESS 2020