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Blood markers can detect early pancreatic cancer
A blood test has been found to be effective for detecting early pancreatic cancer in those at high risk, with the potential to find the deadly cancer at a time when it is more likely to be treatable with surgery, according to phase 2b findings recently published in Science Translational Medicine.
In a 337-person study, researchers found that a blood panel for the protein thrombospondin-2 (THBS2) and cancer antigen 19-9 (CA19-9), measured with a standard ELISA test, together detected pancreatic ductal adenocarcinoma (PDAC) with a specificity of 98% and a sensitivity of 87%. The test was effective at distinguishing patients with PDAC from controls and those with benign pancreatic disease across all stages of the cancer, wrote Kenneth Zaret, PhD, at the University of Pennsylvania, Philadelphia.
CA19-9 is already a known marker for PDAC, but it is a deeply flawed one because it is also elevated in people with nonmalignant pancreatic conditions and can produce false negatives in people without certain antibodies.
But, together, researchers found, THBS2 and CA19-9 make a good pairing for early detection. In the paper, researchers described cases of patients who had no CA19-9 signal at all, likely because they were Lewis-antigen negative, but who had high THBS2 levels. There were also several cases in which THBS2 levels overlapped with the upper end of the normal range but with elevated CA19-9 levels.
“Thus, the two markers appeared to be complementary in their ability to detect PDAC,” Dr. Zaret wrote.
Researchers were able to test for markers by reprogramming advanced PDAC cells to induce a pluripotent stem cell–like state.
Because of the low prevalence of PDAC in the general population, researchers are not recommending the panel as a general screening test.
“We suggest that the THBS2/CA19-9 marker panel could serve as a low-cost, nonintervention screening tool in asymptomatic individuals who have a high risk of developing PDAC,” Dr. Zaret wrote, “and also in patients who are newly diagnosed with diabetes mellitus that developed as a result of pancreatic injury – but not in the general population.”
A blood test has been found to be effective for detecting early pancreatic cancer in those at high risk, with the potential to find the deadly cancer at a time when it is more likely to be treatable with surgery, according to phase 2b findings recently published in Science Translational Medicine.
In a 337-person study, researchers found that a blood panel for the protein thrombospondin-2 (THBS2) and cancer antigen 19-9 (CA19-9), measured with a standard ELISA test, together detected pancreatic ductal adenocarcinoma (PDAC) with a specificity of 98% and a sensitivity of 87%. The test was effective at distinguishing patients with PDAC from controls and those with benign pancreatic disease across all stages of the cancer, wrote Kenneth Zaret, PhD, at the University of Pennsylvania, Philadelphia.
CA19-9 is already a known marker for PDAC, but it is a deeply flawed one because it is also elevated in people with nonmalignant pancreatic conditions and can produce false negatives in people without certain antibodies.
But, together, researchers found, THBS2 and CA19-9 make a good pairing for early detection. In the paper, researchers described cases of patients who had no CA19-9 signal at all, likely because they were Lewis-antigen negative, but who had high THBS2 levels. There were also several cases in which THBS2 levels overlapped with the upper end of the normal range but with elevated CA19-9 levels.
“Thus, the two markers appeared to be complementary in their ability to detect PDAC,” Dr. Zaret wrote.
Researchers were able to test for markers by reprogramming advanced PDAC cells to induce a pluripotent stem cell–like state.
Because of the low prevalence of PDAC in the general population, researchers are not recommending the panel as a general screening test.
“We suggest that the THBS2/CA19-9 marker panel could serve as a low-cost, nonintervention screening tool in asymptomatic individuals who have a high risk of developing PDAC,” Dr. Zaret wrote, “and also in patients who are newly diagnosed with diabetes mellitus that developed as a result of pancreatic injury – but not in the general population.”
A blood test has been found to be effective for detecting early pancreatic cancer in those at high risk, with the potential to find the deadly cancer at a time when it is more likely to be treatable with surgery, according to phase 2b findings recently published in Science Translational Medicine.
In a 337-person study, researchers found that a blood panel for the protein thrombospondin-2 (THBS2) and cancer antigen 19-9 (CA19-9), measured with a standard ELISA test, together detected pancreatic ductal adenocarcinoma (PDAC) with a specificity of 98% and a sensitivity of 87%. The test was effective at distinguishing patients with PDAC from controls and those with benign pancreatic disease across all stages of the cancer, wrote Kenneth Zaret, PhD, at the University of Pennsylvania, Philadelphia.
CA19-9 is already a known marker for PDAC, but it is a deeply flawed one because it is also elevated in people with nonmalignant pancreatic conditions and can produce false negatives in people without certain antibodies.
But, together, researchers found, THBS2 and CA19-9 make a good pairing for early detection. In the paper, researchers described cases of patients who had no CA19-9 signal at all, likely because they were Lewis-antigen negative, but who had high THBS2 levels. There were also several cases in which THBS2 levels overlapped with the upper end of the normal range but with elevated CA19-9 levels.
“Thus, the two markers appeared to be complementary in their ability to detect PDAC,” Dr. Zaret wrote.
Researchers were able to test for markers by reprogramming advanced PDAC cells to induce a pluripotent stem cell–like state.
Because of the low prevalence of PDAC in the general population, researchers are not recommending the panel as a general screening test.
“We suggest that the THBS2/CA19-9 marker panel could serve as a low-cost, nonintervention screening tool in asymptomatic individuals who have a high risk of developing PDAC,” Dr. Zaret wrote, “and also in patients who are newly diagnosed with diabetes mellitus that developed as a result of pancreatic injury – but not in the general population.”
Key clinical point: A blood panel was able to detect pancreatic ductal adenocarcinoma in high-risk people across all stages of their cancer.
Major finding: Using a panel of the protein thrombospondin-2 and cancer antigen 19-9, the specificity was 98% and the sensitivity was 87%.
Data source: A phase 2b study of 337 people, including those at high-risk for PDAC, those with benign pancreatic disease, and control subjects.
Disclosures: Dr. Zaret reported consulting work with BetaLogics/J&J and RaNA Therapeutics.
Antiviral shows early promise for treatment of Zika infection
DENVER – An antiviral drug that is a key player in the recent revolution in the treatment of hepatitis C infection also blocks Zika virus replication both in vitro and in a mouse model, Alysson R. Muotri, PhD, said at the annual meeting of the Teratology Society.
Sofosbuvir is a promising candidate. Not only has it demonstrated efficacy in preclinical work by Dr. Muotri and other groups of investigators, but it is also already a Food and Drug Administration–approved antiviral agent with a relatively reassuring Category B rating for use in pregnancy, meaning no evidence of teratogenicity in animal studies.
Investigators at the Scripps Clinic in La Jolla, Calif., have shown that the replication machinery in the Zika virus genome is closely similar to that of another flavivirus: hepatitis C. Both viruses express an NS2B-NS3 protease essential for generation of functional viral proteins.
“That observation led us to look for drugs that would interact with that replication pocket,” Dr. Muotri said.
The researchers first established in vitro that sofosbuvir can bind to the Zika virus NS2B-NS3 protease interface in an area known as the RNA-directed RNA polymerase domain, both in Zika virus–infected human neural progenitor cells and in cerebral organoids. Next, they demonstrated that sofosbuvir inhibited Zika virus replication in mice in dose-dependent fashion (Antiviral Res. 2017 Jul;143:218-29).
Most recently – and most importantly – the researchers showed that sofosbuvir blocked vertical transmission of Zika virus infection in the mouse model. “It’s neuroprotective for the fetus. There was no PCR [polymerase chain reaction] evidence of Zika virus in the fetal head. Those animals are born normal as far as we can tell,” he said.
The researchers are also engaged in preclinical evaluation of other antiviral agents as potential treatments for Zika infection. Some show even more potent anti-Zika activity than did sofosbuvir. But they have the disadvantage of being nonapproved investigational drugs and hence are far earlier in the developmental pipeline.
Dr. Muotri, whose research is supported by the National Institutes of Health, reported having no relevant financial disclosures.
DENVER – An antiviral drug that is a key player in the recent revolution in the treatment of hepatitis C infection also blocks Zika virus replication both in vitro and in a mouse model, Alysson R. Muotri, PhD, said at the annual meeting of the Teratology Society.
Sofosbuvir is a promising candidate. Not only has it demonstrated efficacy in preclinical work by Dr. Muotri and other groups of investigators, but it is also already a Food and Drug Administration–approved antiviral agent with a relatively reassuring Category B rating for use in pregnancy, meaning no evidence of teratogenicity in animal studies.
Investigators at the Scripps Clinic in La Jolla, Calif., have shown that the replication machinery in the Zika virus genome is closely similar to that of another flavivirus: hepatitis C. Both viruses express an NS2B-NS3 protease essential for generation of functional viral proteins.
“That observation led us to look for drugs that would interact with that replication pocket,” Dr. Muotri said.
The researchers first established in vitro that sofosbuvir can bind to the Zika virus NS2B-NS3 protease interface in an area known as the RNA-directed RNA polymerase domain, both in Zika virus–infected human neural progenitor cells and in cerebral organoids. Next, they demonstrated that sofosbuvir inhibited Zika virus replication in mice in dose-dependent fashion (Antiviral Res. 2017 Jul;143:218-29).
Most recently – and most importantly – the researchers showed that sofosbuvir blocked vertical transmission of Zika virus infection in the mouse model. “It’s neuroprotective for the fetus. There was no PCR [polymerase chain reaction] evidence of Zika virus in the fetal head. Those animals are born normal as far as we can tell,” he said.
The researchers are also engaged in preclinical evaluation of other antiviral agents as potential treatments for Zika infection. Some show even more potent anti-Zika activity than did sofosbuvir. But they have the disadvantage of being nonapproved investigational drugs and hence are far earlier in the developmental pipeline.
Dr. Muotri, whose research is supported by the National Institutes of Health, reported having no relevant financial disclosures.
DENVER – An antiviral drug that is a key player in the recent revolution in the treatment of hepatitis C infection also blocks Zika virus replication both in vitro and in a mouse model, Alysson R. Muotri, PhD, said at the annual meeting of the Teratology Society.
Sofosbuvir is a promising candidate. Not only has it demonstrated efficacy in preclinical work by Dr. Muotri and other groups of investigators, but it is also already a Food and Drug Administration–approved antiviral agent with a relatively reassuring Category B rating for use in pregnancy, meaning no evidence of teratogenicity in animal studies.
Investigators at the Scripps Clinic in La Jolla, Calif., have shown that the replication machinery in the Zika virus genome is closely similar to that of another flavivirus: hepatitis C. Both viruses express an NS2B-NS3 protease essential for generation of functional viral proteins.
“That observation led us to look for drugs that would interact with that replication pocket,” Dr. Muotri said.
The researchers first established in vitro that sofosbuvir can bind to the Zika virus NS2B-NS3 protease interface in an area known as the RNA-directed RNA polymerase domain, both in Zika virus–infected human neural progenitor cells and in cerebral organoids. Next, they demonstrated that sofosbuvir inhibited Zika virus replication in mice in dose-dependent fashion (Antiviral Res. 2017 Jul;143:218-29).
Most recently – and most importantly – the researchers showed that sofosbuvir blocked vertical transmission of Zika virus infection in the mouse model. “It’s neuroprotective for the fetus. There was no PCR [polymerase chain reaction] evidence of Zika virus in the fetal head. Those animals are born normal as far as we can tell,” he said.
The researchers are also engaged in preclinical evaluation of other antiviral agents as potential treatments for Zika infection. Some show even more potent anti-Zika activity than did sofosbuvir. But they have the disadvantage of being nonapproved investigational drugs and hence are far earlier in the developmental pipeline.
Dr. Muotri, whose research is supported by the National Institutes of Health, reported having no relevant financial disclosures.
EXPERT ANALYSIS FROM TERATOLOGY SOCIETY 2017
Firing
Last month’s column on good hiring practices, which stressed the importance of replacing marginal employees with excellent ones, triggered an interesting round of discussion. “Isn’t it true,” asked one contributor, “that most physicians tolerate marginal employees because it’s less painful than firing them?”
Indeed it is. Firing someone is never easy, and it is particularly tough on physicians. Sometimes, however, it is unavoidable if you want to preserve the efficiency and morale of your other employees, as well as your own.
Before you do it, however, be sure that you have legitimate grounds, and assemble as much documentation as you can. Record all terminatable transgressions in the employee’s permanent record, and document all verbal and written warnings. This is essential. You must be prepared to prove that your reasons for termination were legal.
Former employees will sometimes charge that any of a number of their civil rights was violated. For example, federal law prohibits you from firing anyone because of race, gender, national origin, disability, religion, or age (if the employee is over 40). You cannot fire a woman because she is pregnant or recently gave birth. Other illegal reasons include assertion of antidiscrimination rights, refusal to take a lie detector test, and report of OSHA violations.
You also can’t terminate someone for refusing to commit an illegal act, such as filing false insurance claims, or for exercising a legal right, such as voting or participating in a political demonstration. You cannot fire an alcohol abuser unless he or she is caught drinking at work, but many forms of illegal drug use are legitimate cause for termination. Other laws may apply, depending on where you live. When in doubt, contact your state labor department or fair employment office.
If a fired employee alleges that he or she was fired for any of these illegal reasons and you do not have convincing documentation to counter the charge, you may find yourself defending your actions in court. If you anticipate such problems, you can ask the employee to sign a waver of future litigation in exchange for a concession from you – such as extra severance pay or a promise not to contest an unemployment application. Also, consider adding employment practices liability insurance (EPLI) to your umbrella policy, since lawsuits are always a possibility despite all efforts to prevent them.
Once you have all your legal ducks in a row, don’t procrastinate. Get it over with first thing on Monday morning. If you wait until Friday afternoon (as many do), you will worry about the dreaded task all week long, and the fired employee will stew about it all weekend.
Explain the performance you have expected, the steps you have taken to help correct the problems you have seen, and the fact that the problems persist. Try to limit the conversation to a minute or two, have the final paycheck ready, and make it clear that the decision has already been made, so begging and pleading will not change anything.
I’ve been asked to share exactly what I say, so, for what it’s worth: “I have called you in to discuss a difficult issue. You know that we have not been happy with your performance. We are still not happy with it, despite all the discussions we have had, and we feel that you can do better elsewhere. So, today, we will part company, and I wish you the best of luck in your future endeavors. Here is your severance check. I hope there are no hard feelings.”
There will, of course, be hard feelings, but that cannot be helped. The point is to be quick, firm, and decisive. Get it over with and allow everyone to move on.
Be sure to get all your office keys back – or change the locks if you cannot. Back up all important computer files, and change all your passwords. Most employees know more of them than you would ever suspect.
Finally, call the staff together and explain what you have done. They should hear the real story from you, not some distorted version via the rumor mill. You don’t have to explain your reasoning or divulge every detail, but do explain how the termination will affect everyone else. Responsibilities will need to be shifted until a replacement can be hired, and all employees should understand that.
If you are asked in the future to give a reference or write a letter of recommendation for the terminated employee, be sure that everything you say is truthful and well documented.
Last month’s column on good hiring practices, which stressed the importance of replacing marginal employees with excellent ones, triggered an interesting round of discussion. “Isn’t it true,” asked one contributor, “that most physicians tolerate marginal employees because it’s less painful than firing them?”
Indeed it is. Firing someone is never easy, and it is particularly tough on physicians. Sometimes, however, it is unavoidable if you want to preserve the efficiency and morale of your other employees, as well as your own.
Before you do it, however, be sure that you have legitimate grounds, and assemble as much documentation as you can. Record all terminatable transgressions in the employee’s permanent record, and document all verbal and written warnings. This is essential. You must be prepared to prove that your reasons for termination were legal.
Former employees will sometimes charge that any of a number of their civil rights was violated. For example, federal law prohibits you from firing anyone because of race, gender, national origin, disability, religion, or age (if the employee is over 40). You cannot fire a woman because she is pregnant or recently gave birth. Other illegal reasons include assertion of antidiscrimination rights, refusal to take a lie detector test, and report of OSHA violations.
You also can’t terminate someone for refusing to commit an illegal act, such as filing false insurance claims, or for exercising a legal right, such as voting or participating in a political demonstration. You cannot fire an alcohol abuser unless he or she is caught drinking at work, but many forms of illegal drug use are legitimate cause for termination. Other laws may apply, depending on where you live. When in doubt, contact your state labor department or fair employment office.
If a fired employee alleges that he or she was fired for any of these illegal reasons and you do not have convincing documentation to counter the charge, you may find yourself defending your actions in court. If you anticipate such problems, you can ask the employee to sign a waver of future litigation in exchange for a concession from you – such as extra severance pay or a promise not to contest an unemployment application. Also, consider adding employment practices liability insurance (EPLI) to your umbrella policy, since lawsuits are always a possibility despite all efforts to prevent them.
Once you have all your legal ducks in a row, don’t procrastinate. Get it over with first thing on Monday morning. If you wait until Friday afternoon (as many do), you will worry about the dreaded task all week long, and the fired employee will stew about it all weekend.
Explain the performance you have expected, the steps you have taken to help correct the problems you have seen, and the fact that the problems persist. Try to limit the conversation to a minute or two, have the final paycheck ready, and make it clear that the decision has already been made, so begging and pleading will not change anything.
I’ve been asked to share exactly what I say, so, for what it’s worth: “I have called you in to discuss a difficult issue. You know that we have not been happy with your performance. We are still not happy with it, despite all the discussions we have had, and we feel that you can do better elsewhere. So, today, we will part company, and I wish you the best of luck in your future endeavors. Here is your severance check. I hope there are no hard feelings.”
There will, of course, be hard feelings, but that cannot be helped. The point is to be quick, firm, and decisive. Get it over with and allow everyone to move on.
Be sure to get all your office keys back – or change the locks if you cannot. Back up all important computer files, and change all your passwords. Most employees know more of them than you would ever suspect.
Finally, call the staff together and explain what you have done. They should hear the real story from you, not some distorted version via the rumor mill. You don’t have to explain your reasoning or divulge every detail, but do explain how the termination will affect everyone else. Responsibilities will need to be shifted until a replacement can be hired, and all employees should understand that.
If you are asked in the future to give a reference or write a letter of recommendation for the terminated employee, be sure that everything you say is truthful and well documented.
Last month’s column on good hiring practices, which stressed the importance of replacing marginal employees with excellent ones, triggered an interesting round of discussion. “Isn’t it true,” asked one contributor, “that most physicians tolerate marginal employees because it’s less painful than firing them?”
Indeed it is. Firing someone is never easy, and it is particularly tough on physicians. Sometimes, however, it is unavoidable if you want to preserve the efficiency and morale of your other employees, as well as your own.
Before you do it, however, be sure that you have legitimate grounds, and assemble as much documentation as you can. Record all terminatable transgressions in the employee’s permanent record, and document all verbal and written warnings. This is essential. You must be prepared to prove that your reasons for termination were legal.
Former employees will sometimes charge that any of a number of their civil rights was violated. For example, federal law prohibits you from firing anyone because of race, gender, national origin, disability, religion, or age (if the employee is over 40). You cannot fire a woman because she is pregnant or recently gave birth. Other illegal reasons include assertion of antidiscrimination rights, refusal to take a lie detector test, and report of OSHA violations.
You also can’t terminate someone for refusing to commit an illegal act, such as filing false insurance claims, or for exercising a legal right, such as voting or participating in a political demonstration. You cannot fire an alcohol abuser unless he or she is caught drinking at work, but many forms of illegal drug use are legitimate cause for termination. Other laws may apply, depending on where you live. When in doubt, contact your state labor department or fair employment office.
If a fired employee alleges that he or she was fired for any of these illegal reasons and you do not have convincing documentation to counter the charge, you may find yourself defending your actions in court. If you anticipate such problems, you can ask the employee to sign a waver of future litigation in exchange for a concession from you – such as extra severance pay or a promise not to contest an unemployment application. Also, consider adding employment practices liability insurance (EPLI) to your umbrella policy, since lawsuits are always a possibility despite all efforts to prevent them.
Once you have all your legal ducks in a row, don’t procrastinate. Get it over with first thing on Monday morning. If you wait until Friday afternoon (as many do), you will worry about the dreaded task all week long, and the fired employee will stew about it all weekend.
Explain the performance you have expected, the steps you have taken to help correct the problems you have seen, and the fact that the problems persist. Try to limit the conversation to a minute or two, have the final paycheck ready, and make it clear that the decision has already been made, so begging and pleading will not change anything.
I’ve been asked to share exactly what I say, so, for what it’s worth: “I have called you in to discuss a difficult issue. You know that we have not been happy with your performance. We are still not happy with it, despite all the discussions we have had, and we feel that you can do better elsewhere. So, today, we will part company, and I wish you the best of luck in your future endeavors. Here is your severance check. I hope there are no hard feelings.”
There will, of course, be hard feelings, but that cannot be helped. The point is to be quick, firm, and decisive. Get it over with and allow everyone to move on.
Be sure to get all your office keys back – or change the locks if you cannot. Back up all important computer files, and change all your passwords. Most employees know more of them than you would ever suspect.
Finally, call the staff together and explain what you have done. They should hear the real story from you, not some distorted version via the rumor mill. You don’t have to explain your reasoning or divulge every detail, but do explain how the termination will affect everyone else. Responsibilities will need to be shifted until a replacement can be hired, and all employees should understand that.
If you are asked in the future to give a reference or write a letter of recommendation for the terminated employee, be sure that everything you say is truthful and well documented.
Appeals court strikes down Wisconsin medical malpractice cap
An appeals court has struck down Wisconsin’s medical malpractice cap for noneconomic damages, ruling that the $750,000 limit is unconstitutional.
In a July opinion, a panel of the First District Court of Appeals wrote that the medical liability cap denies equal protection for the most severely injured patients who are awarded damages exceeding the limit. The decision reinstates a $16.5 million noneconomic damages verdict awarded to a Wisconsin women who lost her limbs after a delayed sepsis diagnosis, according to court documents.
The Wisconsin Medical Society expressed its disappointment at the decision, warning that the ruling could destabilize Wisconsin’s medical liability environment and endanger patients’ access to high-quality, affordable care.
“This decision endangers the long-term solvency of the Injured Patients and Families Compensation Fund and its ability to adequately compensate patients and incentivizes attorneys to file questionable cases in hopes of astronomical jury awards seen in other states without caps,” Noel Deep, MD, president of the Wisconsin Medical Society, said in a statement. “We look forward to further opportunities to explain the importance of the cap to the stability of Wisconsin’s medical liability environment and its benefits for all Wisconsin patients as this case progresses.”
The Wisconsin Association for Justice, an association for the plaintiffs’ bar, praised the cap’s elimination.
“The Court of Appeals, in a concise and well-reasoned opinion, took a brave step toward ensuring that injured patients in Wisconsin can achieve justice by utilizing their constitutional right to a civil jury trial,” Association President Benjamin S. Wagner said in a statement. “The data the court relied upon speaks for itself. The imposition of damage caps against a person like Ascaris Mayo has no rational relationship to controlling medical costs, nor does the verdict impose a financial hardship on the Injured Patients and Families Compensation Fund. To the contrary, the court’s decision ensures that the fund meets its dual statutory obligations to provide excess insurance to medical professionals and provide compensation to injured patients and families.”
The ruling results from a medical malpractice lawsuit filed by patient Ascaris Mayo and her family against Infinity Health Care in Milwaukee, an emergency physician, a physician assistant, ProAssurance Wisconsin Insurance, and the Wisconsin Injured Patients and Families Compensation Fund. The suit claimed that, during a visit to the emergency department at Columbia St. Mary’s Hospital in Milwaukee for abdominal pain and a high fever, health providers failed to diagnosis and treat Ms. Mayo for sepsis. The sepsis led to organ failure, dry gangrene, and, eventually, amputation of her extremities, according to court documents.
A jury awarded Ms. Mayo and her husband $9 million in economic damages and $16.5 million in noneconomic damages. After the verdict, representatives for the Wisconsin Injured Patients and Families Compensation Fund moved to reduce the noneconomic damages award to $750,000 per the state’s cap. The Mayos challenged the reduction, arguing that the cap violated their constitutional rights. A circuit court concluded that the cap was not facially unconstitutional and that it was unconstitutional as applied to the Mayos because it violated the Mayos’ rights to equal protection and due process. Both the Mayos and representatives for the compensation fund appealed.
In their decision, the appeals panel shot down the reasoning used by Wisconsin’s Legislature to enact the noneconomic damages cap, raising doubts that the limit reduces defensive medicine by physicians and prevents a doctor shortage in the state.
“The record before us does not support a finding that the legislative objectives articulated in [the statute] are promoted in any way because the amount of the noneconomic damages cap is $750,000,” the judges wrote. “Data demonstrate that many states with no caps on noneconomic damages actually have higher physician retention rates than Wisconsin. [In addition,] the record before us shows that the ability to accurately measure the financial impact of ‘defensive medicine’ practices has not improved. ... Indeed, data suggest that the existence of noneconomic damages caps may actually increase the risk to patient safety.”
The case is expected to be appealed to the Wisconsin Supreme Court.
[email protected]
On Twitter @legal_med
An appeals court has struck down Wisconsin’s medical malpractice cap for noneconomic damages, ruling that the $750,000 limit is unconstitutional.
In a July opinion, a panel of the First District Court of Appeals wrote that the medical liability cap denies equal protection for the most severely injured patients who are awarded damages exceeding the limit. The decision reinstates a $16.5 million noneconomic damages verdict awarded to a Wisconsin women who lost her limbs after a delayed sepsis diagnosis, according to court documents.
The Wisconsin Medical Society expressed its disappointment at the decision, warning that the ruling could destabilize Wisconsin’s medical liability environment and endanger patients’ access to high-quality, affordable care.
“This decision endangers the long-term solvency of the Injured Patients and Families Compensation Fund and its ability to adequately compensate patients and incentivizes attorneys to file questionable cases in hopes of astronomical jury awards seen in other states without caps,” Noel Deep, MD, president of the Wisconsin Medical Society, said in a statement. “We look forward to further opportunities to explain the importance of the cap to the stability of Wisconsin’s medical liability environment and its benefits for all Wisconsin patients as this case progresses.”
The Wisconsin Association for Justice, an association for the plaintiffs’ bar, praised the cap’s elimination.
“The Court of Appeals, in a concise and well-reasoned opinion, took a brave step toward ensuring that injured patients in Wisconsin can achieve justice by utilizing their constitutional right to a civil jury trial,” Association President Benjamin S. Wagner said in a statement. “The data the court relied upon speaks for itself. The imposition of damage caps against a person like Ascaris Mayo has no rational relationship to controlling medical costs, nor does the verdict impose a financial hardship on the Injured Patients and Families Compensation Fund. To the contrary, the court’s decision ensures that the fund meets its dual statutory obligations to provide excess insurance to medical professionals and provide compensation to injured patients and families.”
The ruling results from a medical malpractice lawsuit filed by patient Ascaris Mayo and her family against Infinity Health Care in Milwaukee, an emergency physician, a physician assistant, ProAssurance Wisconsin Insurance, and the Wisconsin Injured Patients and Families Compensation Fund. The suit claimed that, during a visit to the emergency department at Columbia St. Mary’s Hospital in Milwaukee for abdominal pain and a high fever, health providers failed to diagnosis and treat Ms. Mayo for sepsis. The sepsis led to organ failure, dry gangrene, and, eventually, amputation of her extremities, according to court documents.
A jury awarded Ms. Mayo and her husband $9 million in economic damages and $16.5 million in noneconomic damages. After the verdict, representatives for the Wisconsin Injured Patients and Families Compensation Fund moved to reduce the noneconomic damages award to $750,000 per the state’s cap. The Mayos challenged the reduction, arguing that the cap violated their constitutional rights. A circuit court concluded that the cap was not facially unconstitutional and that it was unconstitutional as applied to the Mayos because it violated the Mayos’ rights to equal protection and due process. Both the Mayos and representatives for the compensation fund appealed.
In their decision, the appeals panel shot down the reasoning used by Wisconsin’s Legislature to enact the noneconomic damages cap, raising doubts that the limit reduces defensive medicine by physicians and prevents a doctor shortage in the state.
“The record before us does not support a finding that the legislative objectives articulated in [the statute] are promoted in any way because the amount of the noneconomic damages cap is $750,000,” the judges wrote. “Data demonstrate that many states with no caps on noneconomic damages actually have higher physician retention rates than Wisconsin. [In addition,] the record before us shows that the ability to accurately measure the financial impact of ‘defensive medicine’ practices has not improved. ... Indeed, data suggest that the existence of noneconomic damages caps may actually increase the risk to patient safety.”
The case is expected to be appealed to the Wisconsin Supreme Court.
[email protected]
On Twitter @legal_med
An appeals court has struck down Wisconsin’s medical malpractice cap for noneconomic damages, ruling that the $750,000 limit is unconstitutional.
In a July opinion, a panel of the First District Court of Appeals wrote that the medical liability cap denies equal protection for the most severely injured patients who are awarded damages exceeding the limit. The decision reinstates a $16.5 million noneconomic damages verdict awarded to a Wisconsin women who lost her limbs after a delayed sepsis diagnosis, according to court documents.
The Wisconsin Medical Society expressed its disappointment at the decision, warning that the ruling could destabilize Wisconsin’s medical liability environment and endanger patients’ access to high-quality, affordable care.
“This decision endangers the long-term solvency of the Injured Patients and Families Compensation Fund and its ability to adequately compensate patients and incentivizes attorneys to file questionable cases in hopes of astronomical jury awards seen in other states without caps,” Noel Deep, MD, president of the Wisconsin Medical Society, said in a statement. “We look forward to further opportunities to explain the importance of the cap to the stability of Wisconsin’s medical liability environment and its benefits for all Wisconsin patients as this case progresses.”
The Wisconsin Association for Justice, an association for the plaintiffs’ bar, praised the cap’s elimination.
“The Court of Appeals, in a concise and well-reasoned opinion, took a brave step toward ensuring that injured patients in Wisconsin can achieve justice by utilizing their constitutional right to a civil jury trial,” Association President Benjamin S. Wagner said in a statement. “The data the court relied upon speaks for itself. The imposition of damage caps against a person like Ascaris Mayo has no rational relationship to controlling medical costs, nor does the verdict impose a financial hardship on the Injured Patients and Families Compensation Fund. To the contrary, the court’s decision ensures that the fund meets its dual statutory obligations to provide excess insurance to medical professionals and provide compensation to injured patients and families.”
The ruling results from a medical malpractice lawsuit filed by patient Ascaris Mayo and her family against Infinity Health Care in Milwaukee, an emergency physician, a physician assistant, ProAssurance Wisconsin Insurance, and the Wisconsin Injured Patients and Families Compensation Fund. The suit claimed that, during a visit to the emergency department at Columbia St. Mary’s Hospital in Milwaukee for abdominal pain and a high fever, health providers failed to diagnosis and treat Ms. Mayo for sepsis. The sepsis led to organ failure, dry gangrene, and, eventually, amputation of her extremities, according to court documents.
A jury awarded Ms. Mayo and her husband $9 million in economic damages and $16.5 million in noneconomic damages. After the verdict, representatives for the Wisconsin Injured Patients and Families Compensation Fund moved to reduce the noneconomic damages award to $750,000 per the state’s cap. The Mayos challenged the reduction, arguing that the cap violated their constitutional rights. A circuit court concluded that the cap was not facially unconstitutional and that it was unconstitutional as applied to the Mayos because it violated the Mayos’ rights to equal protection and due process. Both the Mayos and representatives for the compensation fund appealed.
In their decision, the appeals panel shot down the reasoning used by Wisconsin’s Legislature to enact the noneconomic damages cap, raising doubts that the limit reduces defensive medicine by physicians and prevents a doctor shortage in the state.
“The record before us does not support a finding that the legislative objectives articulated in [the statute] are promoted in any way because the amount of the noneconomic damages cap is $750,000,” the judges wrote. “Data demonstrate that many states with no caps on noneconomic damages actually have higher physician retention rates than Wisconsin. [In addition,] the record before us shows that the ability to accurately measure the financial impact of ‘defensive medicine’ practices has not improved. ... Indeed, data suggest that the existence of noneconomic damages caps may actually increase the risk to patient safety.”
The case is expected to be appealed to the Wisconsin Supreme Court.
[email protected]
On Twitter @legal_med
Erosive hand OA evades dual IL-1 blocker’s effects
MADRID – Treatment with the dual interleukin (IL) 1 blocker ABT-981 did not improve pain scores or erosive joint damage in patients with hand osteoarthritis (OA) in a phase 2a trial reported at the European Congress of Rheumatology.
The disappointing findings suggest that IL-1 may not be an effective target in erosive hand OA, said Margreet Kloppenburg, MD, of Leiden (the Netherlands) University Medical Center, even though the investigators obtained adequate pharmacodynamic results that suggested it was effectively blocking both IL-1 alpha and IL-1 beta.
The phase 2a, multicenter, randomized, double-blind, placebo-controlled study she reported followed on from a phase 1 trial showing that ABT-981 could dose-dependently reduce neutrophil counts and markers of joint inflammation in patients with knee OA. So it was perhaps natural to see if it could potentially have an effect in patients with erosive hand OA.
The aim of the phase 2a trial was to evaluate the safety and efficacy of ABT-981 in the treatment of 131 patients with erosive hand OA. After screening and a 45-day washout period, patients with confirmed erosive hand OA were randomized to receive ABT-981 200 mg injected every 2 weeks or matching placebo.
The primary endpoint was the change in Australian/Canadian Hand Osteoarthritis Index (AUSCAN) pain from baseline to 16 weeks, but no significant difference was observed. The mean change in AUSCAN pain was –9.2 for the 64 ABT-981-treated patients and –10.7 for placebo-treated patients (P = .039).
“There were similar results with AUSCAN function and tender and swollen joint counts,” Dr. Kloppenburg said.
There were also no differences seen in radiographic or MRI endpoints, such as the number of erosive joints, Kellgren and Lawrence scores, joint-space narrowing, or the presence of osteophytes.
Nevertheless, there was evidence that ABT-981 was decreasing inflammatory markers, such as high-sensitivity C-reactive protein and neutrophils. IL-1 alpha and IL-1 beta were difficult to measure, but data suggested that IL-1 was being blocked.
Disappointing results with cytokine targeting
Hand OA affects around 11% of the OA population and erosive hand OA is a very painful phenotype that affects multiple joints, Xavier Chevalier, MD, of Henri-Mondor Hospital, Paris XII University (France), said during a separate session at the congress.
While there is a rationale for using anti-inflammatory drugs for erosive hand OA, so far there just have not been many, if any, real successes. “The effect sizes are small,” Dr. Chevalier said. “There are not a lot of drugs when compared to hip and knee OA,” he observed.
His general conclusion was that targeting cytokines in hand OA had been “disappointing” with “small effect in subgroup of clinically inflamed IP [interphalangeal] joints.”
Dr. Chevalier questioned: “Is hand OA a real OA?” There are features of the disease that imply it could be more of a ligamentous or enthesitis disease, or perhaps a subchondral bone disorder.
Is erosive hand OA even an inflammatory disease? he asked. Are TNF and IL-1 the right targets? Perhaps not, given the research presented by Dr. Kloppenburg and others, he suggested. Further research needs to look for surrogate markers and try to quantify the structural evolution of the disease, he proposed.
It is important to talk about negative studies and to not make excuses for why they might be negative, Tonia Vincent, PhD, observed during the discussion that followed Dr. Chevalier’s presentation.
“If you do proper, randomized, controlled studies in decent numbers and you don’t see effect sizes, and the only times when you see things are when they are open-label, they are not randomized, you’re looking at small numbers, it just goes to show easy it is to over interpret the results of those small studies,” said Dr. Vincent, professor of musculoskeletal biology at the Kennedy Institute of Rheumatology in Oxford, England.
“My conclusion, from my own in vivo studies and from what you’ve [Dr. Chevalier] just said, is that these are the wrong targets. Just because we are rheumatologists does not mean to say everything is about cytokines,” she said.
AbbVie funded the study. Dr. Kloppenburg acknowledged receiving research support from Pfizer and consultancy fees from AbbVie, GlaxoSmithKline, Merck, and Levicept. Dr. Chevalier disclosed working as an advisor to IBSA [Institut Biochimique SA], Sanofi, and Flexion Therapeutics; as an advisory board member for Laboratoires Genevrier and Labpharma; and receiving travel and accommodation support to attend the meeting from Nordic Pharma. Dr. Vincent did not report her disclosures.
[email protected]
On Twitter @rheumnews1
MADRID – Treatment with the dual interleukin (IL) 1 blocker ABT-981 did not improve pain scores or erosive joint damage in patients with hand osteoarthritis (OA) in a phase 2a trial reported at the European Congress of Rheumatology.
The disappointing findings suggest that IL-1 may not be an effective target in erosive hand OA, said Margreet Kloppenburg, MD, of Leiden (the Netherlands) University Medical Center, even though the investigators obtained adequate pharmacodynamic results that suggested it was effectively blocking both IL-1 alpha and IL-1 beta.
The phase 2a, multicenter, randomized, double-blind, placebo-controlled study she reported followed on from a phase 1 trial showing that ABT-981 could dose-dependently reduce neutrophil counts and markers of joint inflammation in patients with knee OA. So it was perhaps natural to see if it could potentially have an effect in patients with erosive hand OA.
The aim of the phase 2a trial was to evaluate the safety and efficacy of ABT-981 in the treatment of 131 patients with erosive hand OA. After screening and a 45-day washout period, patients with confirmed erosive hand OA were randomized to receive ABT-981 200 mg injected every 2 weeks or matching placebo.
The primary endpoint was the change in Australian/Canadian Hand Osteoarthritis Index (AUSCAN) pain from baseline to 16 weeks, but no significant difference was observed. The mean change in AUSCAN pain was –9.2 for the 64 ABT-981-treated patients and –10.7 for placebo-treated patients (P = .039).
“There were similar results with AUSCAN function and tender and swollen joint counts,” Dr. Kloppenburg said.
There were also no differences seen in radiographic or MRI endpoints, such as the number of erosive joints, Kellgren and Lawrence scores, joint-space narrowing, or the presence of osteophytes.
Nevertheless, there was evidence that ABT-981 was decreasing inflammatory markers, such as high-sensitivity C-reactive protein and neutrophils. IL-1 alpha and IL-1 beta were difficult to measure, but data suggested that IL-1 was being blocked.
Disappointing results with cytokine targeting
Hand OA affects around 11% of the OA population and erosive hand OA is a very painful phenotype that affects multiple joints, Xavier Chevalier, MD, of Henri-Mondor Hospital, Paris XII University (France), said during a separate session at the congress.
While there is a rationale for using anti-inflammatory drugs for erosive hand OA, so far there just have not been many, if any, real successes. “The effect sizes are small,” Dr. Chevalier said. “There are not a lot of drugs when compared to hip and knee OA,” he observed.
His general conclusion was that targeting cytokines in hand OA had been “disappointing” with “small effect in subgroup of clinically inflamed IP [interphalangeal] joints.”
Dr. Chevalier questioned: “Is hand OA a real OA?” There are features of the disease that imply it could be more of a ligamentous or enthesitis disease, or perhaps a subchondral bone disorder.
Is erosive hand OA even an inflammatory disease? he asked. Are TNF and IL-1 the right targets? Perhaps not, given the research presented by Dr. Kloppenburg and others, he suggested. Further research needs to look for surrogate markers and try to quantify the structural evolution of the disease, he proposed.
It is important to talk about negative studies and to not make excuses for why they might be negative, Tonia Vincent, PhD, observed during the discussion that followed Dr. Chevalier’s presentation.
“If you do proper, randomized, controlled studies in decent numbers and you don’t see effect sizes, and the only times when you see things are when they are open-label, they are not randomized, you’re looking at small numbers, it just goes to show easy it is to over interpret the results of those small studies,” said Dr. Vincent, professor of musculoskeletal biology at the Kennedy Institute of Rheumatology in Oxford, England.
“My conclusion, from my own in vivo studies and from what you’ve [Dr. Chevalier] just said, is that these are the wrong targets. Just because we are rheumatologists does not mean to say everything is about cytokines,” she said.
AbbVie funded the study. Dr. Kloppenburg acknowledged receiving research support from Pfizer and consultancy fees from AbbVie, GlaxoSmithKline, Merck, and Levicept. Dr. Chevalier disclosed working as an advisor to IBSA [Institut Biochimique SA], Sanofi, and Flexion Therapeutics; as an advisory board member for Laboratoires Genevrier and Labpharma; and receiving travel and accommodation support to attend the meeting from Nordic Pharma. Dr. Vincent did not report her disclosures.
[email protected]
On Twitter @rheumnews1
MADRID – Treatment with the dual interleukin (IL) 1 blocker ABT-981 did not improve pain scores or erosive joint damage in patients with hand osteoarthritis (OA) in a phase 2a trial reported at the European Congress of Rheumatology.
The disappointing findings suggest that IL-1 may not be an effective target in erosive hand OA, said Margreet Kloppenburg, MD, of Leiden (the Netherlands) University Medical Center, even though the investigators obtained adequate pharmacodynamic results that suggested it was effectively blocking both IL-1 alpha and IL-1 beta.
The phase 2a, multicenter, randomized, double-blind, placebo-controlled study she reported followed on from a phase 1 trial showing that ABT-981 could dose-dependently reduce neutrophil counts and markers of joint inflammation in patients with knee OA. So it was perhaps natural to see if it could potentially have an effect in patients with erosive hand OA.
The aim of the phase 2a trial was to evaluate the safety and efficacy of ABT-981 in the treatment of 131 patients with erosive hand OA. After screening and a 45-day washout period, patients with confirmed erosive hand OA were randomized to receive ABT-981 200 mg injected every 2 weeks or matching placebo.
The primary endpoint was the change in Australian/Canadian Hand Osteoarthritis Index (AUSCAN) pain from baseline to 16 weeks, but no significant difference was observed. The mean change in AUSCAN pain was –9.2 for the 64 ABT-981-treated patients and –10.7 for placebo-treated patients (P = .039).
“There were similar results with AUSCAN function and tender and swollen joint counts,” Dr. Kloppenburg said.
There were also no differences seen in radiographic or MRI endpoints, such as the number of erosive joints, Kellgren and Lawrence scores, joint-space narrowing, or the presence of osteophytes.
Nevertheless, there was evidence that ABT-981 was decreasing inflammatory markers, such as high-sensitivity C-reactive protein and neutrophils. IL-1 alpha and IL-1 beta were difficult to measure, but data suggested that IL-1 was being blocked.
Disappointing results with cytokine targeting
Hand OA affects around 11% of the OA population and erosive hand OA is a very painful phenotype that affects multiple joints, Xavier Chevalier, MD, of Henri-Mondor Hospital, Paris XII University (France), said during a separate session at the congress.
While there is a rationale for using anti-inflammatory drugs for erosive hand OA, so far there just have not been many, if any, real successes. “The effect sizes are small,” Dr. Chevalier said. “There are not a lot of drugs when compared to hip and knee OA,” he observed.
His general conclusion was that targeting cytokines in hand OA had been “disappointing” with “small effect in subgroup of clinically inflamed IP [interphalangeal] joints.”
Dr. Chevalier questioned: “Is hand OA a real OA?” There are features of the disease that imply it could be more of a ligamentous or enthesitis disease, or perhaps a subchondral bone disorder.
Is erosive hand OA even an inflammatory disease? he asked. Are TNF and IL-1 the right targets? Perhaps not, given the research presented by Dr. Kloppenburg and others, he suggested. Further research needs to look for surrogate markers and try to quantify the structural evolution of the disease, he proposed.
It is important to talk about negative studies and to not make excuses for why they might be negative, Tonia Vincent, PhD, observed during the discussion that followed Dr. Chevalier’s presentation.
“If you do proper, randomized, controlled studies in decent numbers and you don’t see effect sizes, and the only times when you see things are when they are open-label, they are not randomized, you’re looking at small numbers, it just goes to show easy it is to over interpret the results of those small studies,” said Dr. Vincent, professor of musculoskeletal biology at the Kennedy Institute of Rheumatology in Oxford, England.
“My conclusion, from my own in vivo studies and from what you’ve [Dr. Chevalier] just said, is that these are the wrong targets. Just because we are rheumatologists does not mean to say everything is about cytokines,” she said.
AbbVie funded the study. Dr. Kloppenburg acknowledged receiving research support from Pfizer and consultancy fees from AbbVie, GlaxoSmithKline, Merck, and Levicept. Dr. Chevalier disclosed working as an advisor to IBSA [Institut Biochimique SA], Sanofi, and Flexion Therapeutics; as an advisory board member for Laboratoires Genevrier and Labpharma; and receiving travel and accommodation support to attend the meeting from Nordic Pharma. Dr. Vincent did not report her disclosures.
[email protected]
On Twitter @rheumnews1
AT THE EULAR 2017 CONGRESS
Key clinical point:
Major finding: The mean change in AUSCAN pain from baseline to week 16 was –9.2 and –10.7 comparing ABT-981 and placebo-treated patients (P = .039).
Data source: A phase 2a, multicenter, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of ABT-981 in the treatment of 131 patients with erosive hand OA.
Disclosures: AbbVie funded the study. The study presenter acknowledged receiving research support from Pfizer and consultancy fees from AbbVie, GlaxoSmithKline, Merck, and Levicept. The other speaker disclosed working as an adviser to IBSA [Institut Biochimique SA], Sanofi, and Flexion Therapeutics; as an advisory board member for Laboratoires Genevrier and Labpharma; and receiving travel and accommodation support to attend the meeting from Nordic Pharma.
Office visit conversations are clues to teens’ predepressive symptoms
SAN FRANCISCO – if you know what to look for, suggest the findings of a qualitative study on teens’ sub-threshold symptoms of depression.
“Probing with sensitive questioning and understanding can help providers assess teens’ risks for depression,” said study coauthor Huma Khan, MD, of the University of Illinois Children’s Hospital in Chicago. “Furthermore, close follow-up with teens who mention certain topics, such as losing interest in activities or the loss of a loved one, also may help providers redirect the trajectory of depressive symptoms.”
To better understand ways in which teens may manifest sub-threshold depressive symptoms and possible coping mechanisms, Dr. Khan’s team conducted a qualitative analysis of 37 hour-long interviews with a subsample of teens enrolled in a larger study for adolescents at risk for depression. The teens, recruited from urban and suburban pediatric clinics, were aged 13-18 years and included 12 from Boston and 25 from Chicago. Ten were Hispanic, 15 were African American, and 12 were white.
The participants qualified for the study based on assessments using the Center for Epidemiological Studies Depression (CESD) scale and two questions about anhedonia and/or a depressed or irritable mood for at least 2 weeks. Teens with a current diagnosis of major depressive disorder or currently receiving therapy for depression were excluded.
Starting without a priori assumptions regarding potential findings, the researchers each independently used codes to identify key concepts in the transcripts and then categorized the codes. During regular meetings, they compared findings and continued until patterns in the content emerged.
The findings revealed that teens often express sadness in ways that don’t necessarily immediately call to mind a risk for depression.
“Our participants rarely described themselves as ‘depressed’ and instead used less specific terms such as ‘stressed’ or ‘down,’ ” Dr. Khan said. “Adolescents spoke of topics including unhappiness with school or family relationships that could be attributed to normal teenage angst by some. However, with further probing, adolescents revealed – in their own words – how profoundly impacted they were by their symptoms in various aspects of their lives.”
The research identified themes in three areas: external negative sources of stress, expressions of sadness, and coping practices. The three main sources of external stress identified included school pressure, family discord, and death of a close friend or family member.
The school pressures included difficulty understanding the material, completing work, passing classes, and achieving set goals. Problems with family ranged from tension and fighting to verbal and emotional abuse as well as stress from specific changes, such as divorce or frequent moves.
The researchers identified four main categories of sadness expression:
• Feeling stressed, sad, or down, often involving crying and interfering with their lives.
• Anger and irritability, often directed at others: One teen said, “Little things annoy me that used not to annoy me.”
• New feelings of apathy: One teen said, “I can still do the stuff I want to do, I just don’t feel like it. I used to love, love singing. Now, I sing, but I don’t really... it’s not all that.”
• Problems sleeping, including difficulty falling or staying asleep or sleeping too much.
“In contrast to the depression screening scales that only indicated sub-threshold depression, adolescents – with further questioning – spoke of significant symptoms of unhappiness, loss of interest in activities, and anger/irritability,” Dr. Khan said. “Some teens had little insight into their feelings.”
For example, statements made by the teens included, “They don’t understand why I’m upset. Sometimes I don’t either,” and “I just got really sad. I don’t know. You cry, but you don’t really know why you’re crying. You’re just crying.”
The adolescents told the researchers that spending time with friends was a major way of dealing with their feelings. In addition, two-thirds of the participants had a health issue that led them to visit their primary care provider or the emergency department. These conditions included asthma, allergies, thyroid issues, attention-deficit/hyperactivity disorder, migraines and headaches, arthritis, ulcers, abdominal pain, colonoscopy, fainting, acne, needing birth control pills, and panic attacks.
The researchers concluded that you need to tune into the feelings teens have through conversations about seemingly innocuous topics, whether it’s an annual check-up or an appointment for a specific concern. The statements and feelings expressed by the teens cut across ethnicities, indicating a possible “universality of symptoms for teens with predepression,” the researchers noted.
“The take-away message of our study is that adolescent providers can play an important role in the prevention of major depressive episodes by heavily relying on individual interviews with patients,” Dr. Khan said. “These conversations are powerful tools in uncovering psychological disturbances that may progress to debilitating depressive episodes if gone unnoticed.”
The research was funded by the National Institutes of Mental Health. Dr. Khan had no relevant financial disclosures.
SAN FRANCISCO – if you know what to look for, suggest the findings of a qualitative study on teens’ sub-threshold symptoms of depression.
“Probing with sensitive questioning and understanding can help providers assess teens’ risks for depression,” said study coauthor Huma Khan, MD, of the University of Illinois Children’s Hospital in Chicago. “Furthermore, close follow-up with teens who mention certain topics, such as losing interest in activities or the loss of a loved one, also may help providers redirect the trajectory of depressive symptoms.”
To better understand ways in which teens may manifest sub-threshold depressive symptoms and possible coping mechanisms, Dr. Khan’s team conducted a qualitative analysis of 37 hour-long interviews with a subsample of teens enrolled in a larger study for adolescents at risk for depression. The teens, recruited from urban and suburban pediatric clinics, were aged 13-18 years and included 12 from Boston and 25 from Chicago. Ten were Hispanic, 15 were African American, and 12 were white.
The participants qualified for the study based on assessments using the Center for Epidemiological Studies Depression (CESD) scale and two questions about anhedonia and/or a depressed or irritable mood for at least 2 weeks. Teens with a current diagnosis of major depressive disorder or currently receiving therapy for depression were excluded.
Starting without a priori assumptions regarding potential findings, the researchers each independently used codes to identify key concepts in the transcripts and then categorized the codes. During regular meetings, they compared findings and continued until patterns in the content emerged.
The findings revealed that teens often express sadness in ways that don’t necessarily immediately call to mind a risk for depression.
“Our participants rarely described themselves as ‘depressed’ and instead used less specific terms such as ‘stressed’ or ‘down,’ ” Dr. Khan said. “Adolescents spoke of topics including unhappiness with school or family relationships that could be attributed to normal teenage angst by some. However, with further probing, adolescents revealed – in their own words – how profoundly impacted they were by their symptoms in various aspects of their lives.”
The research identified themes in three areas: external negative sources of stress, expressions of sadness, and coping practices. The three main sources of external stress identified included school pressure, family discord, and death of a close friend or family member.
The school pressures included difficulty understanding the material, completing work, passing classes, and achieving set goals. Problems with family ranged from tension and fighting to verbal and emotional abuse as well as stress from specific changes, such as divorce or frequent moves.
The researchers identified four main categories of sadness expression:
• Feeling stressed, sad, or down, often involving crying and interfering with their lives.
• Anger and irritability, often directed at others: One teen said, “Little things annoy me that used not to annoy me.”
• New feelings of apathy: One teen said, “I can still do the stuff I want to do, I just don’t feel like it. I used to love, love singing. Now, I sing, but I don’t really... it’s not all that.”
• Problems sleeping, including difficulty falling or staying asleep or sleeping too much.
“In contrast to the depression screening scales that only indicated sub-threshold depression, adolescents – with further questioning – spoke of significant symptoms of unhappiness, loss of interest in activities, and anger/irritability,” Dr. Khan said. “Some teens had little insight into their feelings.”
For example, statements made by the teens included, “They don’t understand why I’m upset. Sometimes I don’t either,” and “I just got really sad. I don’t know. You cry, but you don’t really know why you’re crying. You’re just crying.”
The adolescents told the researchers that spending time with friends was a major way of dealing with their feelings. In addition, two-thirds of the participants had a health issue that led them to visit their primary care provider or the emergency department. These conditions included asthma, allergies, thyroid issues, attention-deficit/hyperactivity disorder, migraines and headaches, arthritis, ulcers, abdominal pain, colonoscopy, fainting, acne, needing birth control pills, and panic attacks.
The researchers concluded that you need to tune into the feelings teens have through conversations about seemingly innocuous topics, whether it’s an annual check-up or an appointment for a specific concern. The statements and feelings expressed by the teens cut across ethnicities, indicating a possible “universality of symptoms for teens with predepression,” the researchers noted.
“The take-away message of our study is that adolescent providers can play an important role in the prevention of major depressive episodes by heavily relying on individual interviews with patients,” Dr. Khan said. “These conversations are powerful tools in uncovering psychological disturbances that may progress to debilitating depressive episodes if gone unnoticed.”
The research was funded by the National Institutes of Mental Health. Dr. Khan had no relevant financial disclosures.
SAN FRANCISCO – if you know what to look for, suggest the findings of a qualitative study on teens’ sub-threshold symptoms of depression.
“Probing with sensitive questioning and understanding can help providers assess teens’ risks for depression,” said study coauthor Huma Khan, MD, of the University of Illinois Children’s Hospital in Chicago. “Furthermore, close follow-up with teens who mention certain topics, such as losing interest in activities or the loss of a loved one, also may help providers redirect the trajectory of depressive symptoms.”
To better understand ways in which teens may manifest sub-threshold depressive symptoms and possible coping mechanisms, Dr. Khan’s team conducted a qualitative analysis of 37 hour-long interviews with a subsample of teens enrolled in a larger study for adolescents at risk for depression. The teens, recruited from urban and suburban pediatric clinics, were aged 13-18 years and included 12 from Boston and 25 from Chicago. Ten were Hispanic, 15 were African American, and 12 were white.
The participants qualified for the study based on assessments using the Center for Epidemiological Studies Depression (CESD) scale and two questions about anhedonia and/or a depressed or irritable mood for at least 2 weeks. Teens with a current diagnosis of major depressive disorder or currently receiving therapy for depression were excluded.
Starting without a priori assumptions regarding potential findings, the researchers each independently used codes to identify key concepts in the transcripts and then categorized the codes. During regular meetings, they compared findings and continued until patterns in the content emerged.
The findings revealed that teens often express sadness in ways that don’t necessarily immediately call to mind a risk for depression.
“Our participants rarely described themselves as ‘depressed’ and instead used less specific terms such as ‘stressed’ or ‘down,’ ” Dr. Khan said. “Adolescents spoke of topics including unhappiness with school or family relationships that could be attributed to normal teenage angst by some. However, with further probing, adolescents revealed – in their own words – how profoundly impacted they were by their symptoms in various aspects of their lives.”
The research identified themes in three areas: external negative sources of stress, expressions of sadness, and coping practices. The three main sources of external stress identified included school pressure, family discord, and death of a close friend or family member.
The school pressures included difficulty understanding the material, completing work, passing classes, and achieving set goals. Problems with family ranged from tension and fighting to verbal and emotional abuse as well as stress from specific changes, such as divorce or frequent moves.
The researchers identified four main categories of sadness expression:
• Feeling stressed, sad, or down, often involving crying and interfering with their lives.
• Anger and irritability, often directed at others: One teen said, “Little things annoy me that used not to annoy me.”
• New feelings of apathy: One teen said, “I can still do the stuff I want to do, I just don’t feel like it. I used to love, love singing. Now, I sing, but I don’t really... it’s not all that.”
• Problems sleeping, including difficulty falling or staying asleep or sleeping too much.
“In contrast to the depression screening scales that only indicated sub-threshold depression, adolescents – with further questioning – spoke of significant symptoms of unhappiness, loss of interest in activities, and anger/irritability,” Dr. Khan said. “Some teens had little insight into their feelings.”
For example, statements made by the teens included, “They don’t understand why I’m upset. Sometimes I don’t either,” and “I just got really sad. I don’t know. You cry, but you don’t really know why you’re crying. You’re just crying.”
The adolescents told the researchers that spending time with friends was a major way of dealing with their feelings. In addition, two-thirds of the participants had a health issue that led them to visit their primary care provider or the emergency department. These conditions included asthma, allergies, thyroid issues, attention-deficit/hyperactivity disorder, migraines and headaches, arthritis, ulcers, abdominal pain, colonoscopy, fainting, acne, needing birth control pills, and panic attacks.
The researchers concluded that you need to tune into the feelings teens have through conversations about seemingly innocuous topics, whether it’s an annual check-up or an appointment for a specific concern. The statements and feelings expressed by the teens cut across ethnicities, indicating a possible “universality of symptoms for teens with predepression,” the researchers noted.
“The take-away message of our study is that adolescent providers can play an important role in the prevention of major depressive episodes by heavily relying on individual interviews with patients,” Dr. Khan said. “These conversations are powerful tools in uncovering psychological disturbances that may progress to debilitating depressive episodes if gone unnoticed.”
The research was funded by the National Institutes of Mental Health. Dr. Khan had no relevant financial disclosures.
AT PAS 17
Key clinical point: Dialogue with teens at each visit may reveal predepressive symptoms indicating an opportunity for depression prevention.
Major finding: The research identified themes in three areas: external negative sources of stress, expressions of sadness, and coping practices. The three main sources of external stress identified included school pressure, family discord, and death of a close friend or family member.
Data source: The findings are based on a qualitative analysis of 37 K-SADS interviews with teens aged 13-18 years from Chicago and Boston community pediatric clinics.
Disclosures: The research was funded by the National Institutes of Mental Health. Dr. Khan had no relevant financial disclosures.
Expert: Engage patients, clinicians as partners in research
MIAMI – Not all researchers are clinicians, but what if all clinicians were researchers? Clinical studies would yield more relevant data, resulting in better patient care, according to an expert.
“The clinical research enterprise is broken,” Andrew A. Nierenberg, MD, said during a keynote plenary session dedicated to serving diverse populations, at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting. “It’s a problem, because it really does not have an impact on the actual care we give, and it doesn’t answer the types of questions that patients care about.”
One persistent problem, Dr. Nierenberg said, is that often those who enroll in trials have unclear motives for doing so, but those motives usually are tied to incentives such as cash. “Who goes into these trials and why is absolutely critical to the signal,” he said.
Questionable intent is compounded by inadequate or nonexistent explanations to study participants about the researchers’ reasons for the trial, and no clear justification for why the participants should adhere to the protocols. This leads to medications often not being taken as directed, and poor attendance at follow-up points and psychosocial visits. The result overall, he said, is that clinical research amounts to symptomatic volunteers who are strangers to the investigator “doing weird things in places where they have never been before and [not really understanding] why they are doing them.” In practical terms, this means that the amount of evidence-based medicine practiced across the specialties is low – only about 15%, said Dr. Nierenberg, who cited a study that pinned blame for the “fragmented ‘nonsystem’ of [clinical research] on a lack of common goals, vision, and collaboration” (JAMA. 2009;301[8]:831-41).
The best solution would be integrating the clinical and the research enterprises into a single system – where patients and clinicians alike are engaged in the research process, he said.
“Transform clinicians into partners and collaborators. Engage them up front to help recruit, not just for your study but for all studies,” said Dr. Nierenberg, the incumbent holder of the Thomas P. Hackett, MD Endowed Chair in Psychiatry at Massachusetts General Hospital in Boston. “If someone comes in [seeking treatment], they can opt out of doing research, but the assumption is that they will collaborate and that we will expect them to collaborate.”
In his own work, Dr. Nierenberg helps run the MoodNetwork, a growing, nationwide database of patient-reported outcomes for those with mood disorders that he said is dedicated to filling knowledge gaps around those illnesses not easily gleaned from clinical response data alone. “Patients know what it is like to live with their illness more than we do,” said Dr. Nierenberg, also director of the Dauten Family Center for Bipolar Treatment Innovation in Boston.
The data from the MoodNetwork also feed into a nationwide network of databases run by the Patient-Centered Outcomes Research Institute network, originally created as part of the Affordable Care Act, and which, at least for now, Dr. Nierenberg said, appears safe from repeal. The network recently received $28 million to help create the necessary infrastructure for connecting research and clinical databases – including the electronic health records – from a variety of health institutions nationwide. “Most of you have your EHRs embedded into those networks even if you don’t know it,” Dr. Nierenberg said.
PCORInet’s resulting uber-database currently has patient-reported data on more than 122 million people. All of the data are queryable and available for use for virtually any study a clinical researcher or clinician would like to conduct into any aspect of any clinical specialty.
In his clinical practice, Dr. Nierenberg said, he is able to solicit patients in MoodNetwork studies by appealing to them as partners and collaborators from the moment they present in the clinic. He and his colleagues ensure that patients understand the importance of their participation not just to them as sufferers of an illness, but to the care of millions of others. Key to working together as partners is to use plain language when explaining treatment and research goals. It also is important to survey patients and listen to them when they share their experience of trials and treatment.
“We tend to suffer from the curse of knowledge,” Dr. Nierenberg said, referring to the amount of technical jargon that often separates study participants from researchers. “We are so embedded in our world; we can’t imagine not understanding it. It’s a failure to communicate, and it happens over and over again.”
Dr. Nierenberg’s talk generated buzz days after he gave it. During the meeting’s final regulatory plenary session, ASCP President Mark H. Rapaport, MD, chair of psychiatry and behavioral sciences at Emory University in Atlanta, invited Dr. Nierenberg to help clarify for Food and Drug Administration officials and attendees alike the extent to which point-of-care research could avoid numerous pitfalls, including expectation bias and an outsized placebo effect – two drawbacks that researchers typically avoid by purposefully not interacting with patients.
The way around those confounders, Dr. Nierenberg said, is to begin communicating with patients as soon as they enter the clinic. Randomize those who are seeking care from those who are willing to participate in research for a time-limited duration, and emphasize that there is continuity before and after the research with the same clinician providing the clinical care. “Be very explicit in saying to them that: ‘The study might affect your care and the care of others in the future, but that it is just as important to the study if you don’t respond as if you do [respond].’ ”
To avoid rater bias, he suggested blinding raters as to which clinicians gathered the data on which patients.
Incentivizing clinicians to change their work flows to accommodate becoming researchers requires seeing them as equals. As the current system of research is now, Dr. Nierenberg said, “clinicians get pushed aside.” Instead, he suggested, meet clinicians’ desires for access to the data to help care for their patients, or CMEs, and webinars – all resources and tools he said were possible to achieve with dashboards built into the information networks.
Dr. Nierenberg talked about the importance of teaching patients how to be collaborators, such as by having them respond to practice questions, asking whether they understand what is being asked of them, and presenting them with videos about what to expect.
Conversely, the patient can teach the researcher how to be a better collaborator. During the regulatory plenary session, Dr. Rapaport called upon David Sheehan, MD, a distinguished university health professor emeritus at University of South Florida in Tampa, now in private practice. His Sheehan Suicidality Tracking Scale was validated in a study that described the scale as having “excellent accuracy for suicidal ideation” (J Clin Psychiatry. 2015 Dec;76[12]:1676-82).
Throughout his career, Dr. Sheehan said, he has asked his patients to arrive early to their appointments to answer questions on scales of his own creation. He then reviews them with the patient in each visit and asks for their feedback. “Honestly, they gave me the best advice ...” Dr. Sheehan said. “It’s the way they phrase the questions that I would never would have thought up. They would say to me, ‘We would understand [the questions] if you put them this way, but if you don’t change the wording, a whole cohort of your patients will give you the wrong kind of answer.’ With decades of input like that, I realized it was the best way to go.”
Dr. Nierenberg described an alchemy of sorts that occurs when the power differential between the holder of the learned knowledge (the researcher) and the holder of experiential knowledge (the patient) is bridged. “What happens to your attitude when you’re working with a ‘collaborator’ compared to when you are working with a ‘patient’? You feel it, but you’re unaware of the bias. But if you think of them as your partners, and tell them that they are, you find they shift. They own it. It’s an authentic engagement over time.”
Ultimately, better research will lead to better patient care, he said.
Dr. Nierenberg had no relevant disclosures.
[email protected]
On Twitter @whitneymcknight
MIAMI – Not all researchers are clinicians, but what if all clinicians were researchers? Clinical studies would yield more relevant data, resulting in better patient care, according to an expert.
“The clinical research enterprise is broken,” Andrew A. Nierenberg, MD, said during a keynote plenary session dedicated to serving diverse populations, at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting. “It’s a problem, because it really does not have an impact on the actual care we give, and it doesn’t answer the types of questions that patients care about.”
One persistent problem, Dr. Nierenberg said, is that often those who enroll in trials have unclear motives for doing so, but those motives usually are tied to incentives such as cash. “Who goes into these trials and why is absolutely critical to the signal,” he said.
Questionable intent is compounded by inadequate or nonexistent explanations to study participants about the researchers’ reasons for the trial, and no clear justification for why the participants should adhere to the protocols. This leads to medications often not being taken as directed, and poor attendance at follow-up points and psychosocial visits. The result overall, he said, is that clinical research amounts to symptomatic volunteers who are strangers to the investigator “doing weird things in places where they have never been before and [not really understanding] why they are doing them.” In practical terms, this means that the amount of evidence-based medicine practiced across the specialties is low – only about 15%, said Dr. Nierenberg, who cited a study that pinned blame for the “fragmented ‘nonsystem’ of [clinical research] on a lack of common goals, vision, and collaboration” (JAMA. 2009;301[8]:831-41).
The best solution would be integrating the clinical and the research enterprises into a single system – where patients and clinicians alike are engaged in the research process, he said.
“Transform clinicians into partners and collaborators. Engage them up front to help recruit, not just for your study but for all studies,” said Dr. Nierenberg, the incumbent holder of the Thomas P. Hackett, MD Endowed Chair in Psychiatry at Massachusetts General Hospital in Boston. “If someone comes in [seeking treatment], they can opt out of doing research, but the assumption is that they will collaborate and that we will expect them to collaborate.”
In his own work, Dr. Nierenberg helps run the MoodNetwork, a growing, nationwide database of patient-reported outcomes for those with mood disorders that he said is dedicated to filling knowledge gaps around those illnesses not easily gleaned from clinical response data alone. “Patients know what it is like to live with their illness more than we do,” said Dr. Nierenberg, also director of the Dauten Family Center for Bipolar Treatment Innovation in Boston.
The data from the MoodNetwork also feed into a nationwide network of databases run by the Patient-Centered Outcomes Research Institute network, originally created as part of the Affordable Care Act, and which, at least for now, Dr. Nierenberg said, appears safe from repeal. The network recently received $28 million to help create the necessary infrastructure for connecting research and clinical databases – including the electronic health records – from a variety of health institutions nationwide. “Most of you have your EHRs embedded into those networks even if you don’t know it,” Dr. Nierenberg said.
PCORInet’s resulting uber-database currently has patient-reported data on more than 122 million people. All of the data are queryable and available for use for virtually any study a clinical researcher or clinician would like to conduct into any aspect of any clinical specialty.
In his clinical practice, Dr. Nierenberg said, he is able to solicit patients in MoodNetwork studies by appealing to them as partners and collaborators from the moment they present in the clinic. He and his colleagues ensure that patients understand the importance of their participation not just to them as sufferers of an illness, but to the care of millions of others. Key to working together as partners is to use plain language when explaining treatment and research goals. It also is important to survey patients and listen to them when they share their experience of trials and treatment.
“We tend to suffer from the curse of knowledge,” Dr. Nierenberg said, referring to the amount of technical jargon that often separates study participants from researchers. “We are so embedded in our world; we can’t imagine not understanding it. It’s a failure to communicate, and it happens over and over again.”
Dr. Nierenberg’s talk generated buzz days after he gave it. During the meeting’s final regulatory plenary session, ASCP President Mark H. Rapaport, MD, chair of psychiatry and behavioral sciences at Emory University in Atlanta, invited Dr. Nierenberg to help clarify for Food and Drug Administration officials and attendees alike the extent to which point-of-care research could avoid numerous pitfalls, including expectation bias and an outsized placebo effect – two drawbacks that researchers typically avoid by purposefully not interacting with patients.
The way around those confounders, Dr. Nierenberg said, is to begin communicating with patients as soon as they enter the clinic. Randomize those who are seeking care from those who are willing to participate in research for a time-limited duration, and emphasize that there is continuity before and after the research with the same clinician providing the clinical care. “Be very explicit in saying to them that: ‘The study might affect your care and the care of others in the future, but that it is just as important to the study if you don’t respond as if you do [respond].’ ”
To avoid rater bias, he suggested blinding raters as to which clinicians gathered the data on which patients.
Incentivizing clinicians to change their work flows to accommodate becoming researchers requires seeing them as equals. As the current system of research is now, Dr. Nierenberg said, “clinicians get pushed aside.” Instead, he suggested, meet clinicians’ desires for access to the data to help care for their patients, or CMEs, and webinars – all resources and tools he said were possible to achieve with dashboards built into the information networks.
Dr. Nierenberg talked about the importance of teaching patients how to be collaborators, such as by having them respond to practice questions, asking whether they understand what is being asked of them, and presenting them with videos about what to expect.
Conversely, the patient can teach the researcher how to be a better collaborator. During the regulatory plenary session, Dr. Rapaport called upon David Sheehan, MD, a distinguished university health professor emeritus at University of South Florida in Tampa, now in private practice. His Sheehan Suicidality Tracking Scale was validated in a study that described the scale as having “excellent accuracy for suicidal ideation” (J Clin Psychiatry. 2015 Dec;76[12]:1676-82).
Throughout his career, Dr. Sheehan said, he has asked his patients to arrive early to their appointments to answer questions on scales of his own creation. He then reviews them with the patient in each visit and asks for their feedback. “Honestly, they gave me the best advice ...” Dr. Sheehan said. “It’s the way they phrase the questions that I would never would have thought up. They would say to me, ‘We would understand [the questions] if you put them this way, but if you don’t change the wording, a whole cohort of your patients will give you the wrong kind of answer.’ With decades of input like that, I realized it was the best way to go.”
Dr. Nierenberg described an alchemy of sorts that occurs when the power differential between the holder of the learned knowledge (the researcher) and the holder of experiential knowledge (the patient) is bridged. “What happens to your attitude when you’re working with a ‘collaborator’ compared to when you are working with a ‘patient’? You feel it, but you’re unaware of the bias. But if you think of them as your partners, and tell them that they are, you find they shift. They own it. It’s an authentic engagement over time.”
Ultimately, better research will lead to better patient care, he said.
Dr. Nierenberg had no relevant disclosures.
[email protected]
On Twitter @whitneymcknight
MIAMI – Not all researchers are clinicians, but what if all clinicians were researchers? Clinical studies would yield more relevant data, resulting in better patient care, according to an expert.
“The clinical research enterprise is broken,” Andrew A. Nierenberg, MD, said during a keynote plenary session dedicated to serving diverse populations, at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting. “It’s a problem, because it really does not have an impact on the actual care we give, and it doesn’t answer the types of questions that patients care about.”
One persistent problem, Dr. Nierenberg said, is that often those who enroll in trials have unclear motives for doing so, but those motives usually are tied to incentives such as cash. “Who goes into these trials and why is absolutely critical to the signal,” he said.
Questionable intent is compounded by inadequate or nonexistent explanations to study participants about the researchers’ reasons for the trial, and no clear justification for why the participants should adhere to the protocols. This leads to medications often not being taken as directed, and poor attendance at follow-up points and psychosocial visits. The result overall, he said, is that clinical research amounts to symptomatic volunteers who are strangers to the investigator “doing weird things in places where they have never been before and [not really understanding] why they are doing them.” In practical terms, this means that the amount of evidence-based medicine practiced across the specialties is low – only about 15%, said Dr. Nierenberg, who cited a study that pinned blame for the “fragmented ‘nonsystem’ of [clinical research] on a lack of common goals, vision, and collaboration” (JAMA. 2009;301[8]:831-41).
The best solution would be integrating the clinical and the research enterprises into a single system – where patients and clinicians alike are engaged in the research process, he said.
“Transform clinicians into partners and collaborators. Engage them up front to help recruit, not just for your study but for all studies,” said Dr. Nierenberg, the incumbent holder of the Thomas P. Hackett, MD Endowed Chair in Psychiatry at Massachusetts General Hospital in Boston. “If someone comes in [seeking treatment], they can opt out of doing research, but the assumption is that they will collaborate and that we will expect them to collaborate.”
In his own work, Dr. Nierenberg helps run the MoodNetwork, a growing, nationwide database of patient-reported outcomes for those with mood disorders that he said is dedicated to filling knowledge gaps around those illnesses not easily gleaned from clinical response data alone. “Patients know what it is like to live with their illness more than we do,” said Dr. Nierenberg, also director of the Dauten Family Center for Bipolar Treatment Innovation in Boston.
The data from the MoodNetwork also feed into a nationwide network of databases run by the Patient-Centered Outcomes Research Institute network, originally created as part of the Affordable Care Act, and which, at least for now, Dr. Nierenberg said, appears safe from repeal. The network recently received $28 million to help create the necessary infrastructure for connecting research and clinical databases – including the electronic health records – from a variety of health institutions nationwide. “Most of you have your EHRs embedded into those networks even if you don’t know it,” Dr. Nierenberg said.
PCORInet’s resulting uber-database currently has patient-reported data on more than 122 million people. All of the data are queryable and available for use for virtually any study a clinical researcher or clinician would like to conduct into any aspect of any clinical specialty.
In his clinical practice, Dr. Nierenberg said, he is able to solicit patients in MoodNetwork studies by appealing to them as partners and collaborators from the moment they present in the clinic. He and his colleagues ensure that patients understand the importance of their participation not just to them as sufferers of an illness, but to the care of millions of others. Key to working together as partners is to use plain language when explaining treatment and research goals. It also is important to survey patients and listen to them when they share their experience of trials and treatment.
“We tend to suffer from the curse of knowledge,” Dr. Nierenberg said, referring to the amount of technical jargon that often separates study participants from researchers. “We are so embedded in our world; we can’t imagine not understanding it. It’s a failure to communicate, and it happens over and over again.”
Dr. Nierenberg’s talk generated buzz days after he gave it. During the meeting’s final regulatory plenary session, ASCP President Mark H. Rapaport, MD, chair of psychiatry and behavioral sciences at Emory University in Atlanta, invited Dr. Nierenberg to help clarify for Food and Drug Administration officials and attendees alike the extent to which point-of-care research could avoid numerous pitfalls, including expectation bias and an outsized placebo effect – two drawbacks that researchers typically avoid by purposefully not interacting with patients.
The way around those confounders, Dr. Nierenberg said, is to begin communicating with patients as soon as they enter the clinic. Randomize those who are seeking care from those who are willing to participate in research for a time-limited duration, and emphasize that there is continuity before and after the research with the same clinician providing the clinical care. “Be very explicit in saying to them that: ‘The study might affect your care and the care of others in the future, but that it is just as important to the study if you don’t respond as if you do [respond].’ ”
To avoid rater bias, he suggested blinding raters as to which clinicians gathered the data on which patients.
Incentivizing clinicians to change their work flows to accommodate becoming researchers requires seeing them as equals. As the current system of research is now, Dr. Nierenberg said, “clinicians get pushed aside.” Instead, he suggested, meet clinicians’ desires for access to the data to help care for their patients, or CMEs, and webinars – all resources and tools he said were possible to achieve with dashboards built into the information networks.
Dr. Nierenberg talked about the importance of teaching patients how to be collaborators, such as by having them respond to practice questions, asking whether they understand what is being asked of them, and presenting them with videos about what to expect.
Conversely, the patient can teach the researcher how to be a better collaborator. During the regulatory plenary session, Dr. Rapaport called upon David Sheehan, MD, a distinguished university health professor emeritus at University of South Florida in Tampa, now in private practice. His Sheehan Suicidality Tracking Scale was validated in a study that described the scale as having “excellent accuracy for suicidal ideation” (J Clin Psychiatry. 2015 Dec;76[12]:1676-82).
Throughout his career, Dr. Sheehan said, he has asked his patients to arrive early to their appointments to answer questions on scales of his own creation. He then reviews them with the patient in each visit and asks for their feedback. “Honestly, they gave me the best advice ...” Dr. Sheehan said. “It’s the way they phrase the questions that I would never would have thought up. They would say to me, ‘We would understand [the questions] if you put them this way, but if you don’t change the wording, a whole cohort of your patients will give you the wrong kind of answer.’ With decades of input like that, I realized it was the best way to go.”
Dr. Nierenberg described an alchemy of sorts that occurs when the power differential between the holder of the learned knowledge (the researcher) and the holder of experiential knowledge (the patient) is bridged. “What happens to your attitude when you’re working with a ‘collaborator’ compared to when you are working with a ‘patient’? You feel it, but you’re unaware of the bias. But if you think of them as your partners, and tell them that they are, you find they shift. They own it. It’s an authentic engagement over time.”
Ultimately, better research will lead to better patient care, he said.
Dr. Nierenberg had no relevant disclosures.
[email protected]
On Twitter @whitneymcknight
EXPERT ANALYSIS FROM THE ASCP ANNUAL MEETING
Preventing Zika in pregnancy: What you need to know
DENVER – Prevention of Zika virus infection in pregnancy is critical, given the lack of an effective treatment or vaccine, but it’s easier said than done.
“The particular mosquito that transmits Zika is really difficult because it tends to be indoors and live under the coffee table in your living room rather than outside. It bites in the day, as well as night, so it’s hard to prevent. Trying to consistently have repellent on [and] wear long-sleeved shirts and long pants, even when you’re indoors, in places that are typically quite warm – it’s challenging,” Margaret Honein, PhD, said at the annual meeting of the Teratology Society.
The CDC’s top Zika prevention advice is that pregnant women should not travel to any area where Zika is a risk. If they absolutely have to go, they should talk to their health care provider first, strictly follow measures to prevent mosquito bites during the trip, take steps to prevent sexual transmission – namely, use a condom – and talk with their health care provider once again upon their return.
It is now clear that Zika can be transmitted sexually. For this reason, even a pregnant woman who doesn’t visit an area with Zika risk, but whose partner has been to such a place, must also practice safe sex using a condom, even if the partner is asymptomatic.
In response to an audience question from a Washington, D.C.–area ob.gyn. who noted that there isn’t a Zika problem in his region, Dr. Honein said that her personal view is that pregnant women living in the vicinity of the nation’s capitol should also follow the CDC recommendations for travelers to, or residents of, areas where Zika is found.
“You have mosquito vectors that can transmit Zika in Washington, D.C., and a lot of other parts of the country,” she said. “There are travelers coming back from areas with risk for Zika all the time. If they get bit by a mosquito, which then bites another person and transmits the infection, there’s a problem. So, for pregnant women in areas that have a mosquito vector that can transmit the virus, I think it’s very wise advice to consistently use mosquito repellent and take the other protective measures. People should be doing everything they can to protect against Zika infection in pregnancy.”
DENVER – Prevention of Zika virus infection in pregnancy is critical, given the lack of an effective treatment or vaccine, but it’s easier said than done.
“The particular mosquito that transmits Zika is really difficult because it tends to be indoors and live under the coffee table in your living room rather than outside. It bites in the day, as well as night, so it’s hard to prevent. Trying to consistently have repellent on [and] wear long-sleeved shirts and long pants, even when you’re indoors, in places that are typically quite warm – it’s challenging,” Margaret Honein, PhD, said at the annual meeting of the Teratology Society.
The CDC’s top Zika prevention advice is that pregnant women should not travel to any area where Zika is a risk. If they absolutely have to go, they should talk to their health care provider first, strictly follow measures to prevent mosquito bites during the trip, take steps to prevent sexual transmission – namely, use a condom – and talk with their health care provider once again upon their return.
It is now clear that Zika can be transmitted sexually. For this reason, even a pregnant woman who doesn’t visit an area with Zika risk, but whose partner has been to such a place, must also practice safe sex using a condom, even if the partner is asymptomatic.
In response to an audience question from a Washington, D.C.–area ob.gyn. who noted that there isn’t a Zika problem in his region, Dr. Honein said that her personal view is that pregnant women living in the vicinity of the nation’s capitol should also follow the CDC recommendations for travelers to, or residents of, areas where Zika is found.
“You have mosquito vectors that can transmit Zika in Washington, D.C., and a lot of other parts of the country,” she said. “There are travelers coming back from areas with risk for Zika all the time. If they get bit by a mosquito, which then bites another person and transmits the infection, there’s a problem. So, for pregnant women in areas that have a mosquito vector that can transmit the virus, I think it’s very wise advice to consistently use mosquito repellent and take the other protective measures. People should be doing everything they can to protect against Zika infection in pregnancy.”
DENVER – Prevention of Zika virus infection in pregnancy is critical, given the lack of an effective treatment or vaccine, but it’s easier said than done.
“The particular mosquito that transmits Zika is really difficult because it tends to be indoors and live under the coffee table in your living room rather than outside. It bites in the day, as well as night, so it’s hard to prevent. Trying to consistently have repellent on [and] wear long-sleeved shirts and long pants, even when you’re indoors, in places that are typically quite warm – it’s challenging,” Margaret Honein, PhD, said at the annual meeting of the Teratology Society.
The CDC’s top Zika prevention advice is that pregnant women should not travel to any area where Zika is a risk. If they absolutely have to go, they should talk to their health care provider first, strictly follow measures to prevent mosquito bites during the trip, take steps to prevent sexual transmission – namely, use a condom – and talk with their health care provider once again upon their return.
It is now clear that Zika can be transmitted sexually. For this reason, even a pregnant woman who doesn’t visit an area with Zika risk, but whose partner has been to such a place, must also practice safe sex using a condom, even if the partner is asymptomatic.
In response to an audience question from a Washington, D.C.–area ob.gyn. who noted that there isn’t a Zika problem in his region, Dr. Honein said that her personal view is that pregnant women living in the vicinity of the nation’s capitol should also follow the CDC recommendations for travelers to, or residents of, areas where Zika is found.
“You have mosquito vectors that can transmit Zika in Washington, D.C., and a lot of other parts of the country,” she said. “There are travelers coming back from areas with risk for Zika all the time. If they get bit by a mosquito, which then bites another person and transmits the infection, there’s a problem. So, for pregnant women in areas that have a mosquito vector that can transmit the virus, I think it’s very wise advice to consistently use mosquito repellent and take the other protective measures. People should be doing everything they can to protect against Zika infection in pregnancy.”
EXPERT ANALYSIS FROM TERATOLOGY SOCIETY 2017
Asymptomatic maternal Zika infection doesn’t dampen birth defect risk
DENVER – One of many daunting challenges posed by the ongoing global Zika virus epidemic stems from the recent realization that the presence or absence of symptoms in women infected in pregnancy has no bearing on whether their babies will have Zika-associated birth defects, Margaret Honein, PhD, observed at the annual meeting of the Teratology Society.
This has profound clinical consequences because roughly 80% of all maternal Zika infections are asymptomatic or feature such mild symptoms that women don’t report them.
“There was, I think, some hope early on that symptoms in the mother would correlate with outcomes, but that has not been the case at all. In the U.S. population, we’ve seen about a 6% Zika-associated birth defects rate in both symptomatic and asymptomatic mothers,” said Dr. Honein, chief of the birth defects branch at the Centers for Disease Control and Prevention in Atlanta. “We have a huge challenge in identifying the women who have asymptomatic infections, yet they’re at the same risk of having an adverse outcome in their baby.”[[{"fid":"199780","view_mode":"medstat_image_flush_right","fields":
She provided conference attendees with the latest information on Zika, including preliminary results from ongoing CDC investigations. Along the way, she tackled many of the questions Zika experts hear most often from clinicians, while emphasizing that much about congenital Zika syndrome remains unknown.
Just how serious is the global threat of Zika virus infection?
On Feb. 8, 2016, the CDC activated a Level 1 emergency response to Zika. To put that into perspective, this is only the fourth time in history the agency has gone to Level 1. The other occasions were for Hurricane Katrina, the H1N1 pandemic flu, and Ebola.
“This is worse than thalidomide,” said Jan M. Friedman, MD, after listening to Dr. Honein and other speakers at the Zika update held during the conference. Dr. Friedman, a medical geneticist at the University of British Columbia, Vancouver, delivered the Robert L. Brent Lecture.
What is the level of risk for fetal/infant birth defects associated with maternal Zika virus infection?
The birth defect risk is somewhere between 5% and 10%, with the true figure probably being on the high end. Reports quoting risks on the lower end are based upon laboratory testing for maternal IgM antibodies, which couldn’t rule out cross reaction with other flaviviruses, including dengue virus, which is common in most of the same locales as Zika. Women who have been infected with dengue but not Zika are not at increased risk for birth defects. Zika is the first mosquito-borne virus to be recognized as teratogenic in humans.
The birth defects seen in conjunction with Zika infection are not unique. They can have many different causes. CDC investigators examined birth defects data from three states during the year before the Zika outbreak in the Western Hemisphere and determined that the background rate of microcephaly, neural tube defects, eye abnormalities, hearing loss, and other Zika-like birth defects was 3 per 1,000 live births. Among women with Zika virus infection in pregnancy, however, the rate is more than 20-fold higher at 50-100 per 1,000, according to Dr. Honein.
When during pregnancy does maternal Zika infection pose the highest risk to the fetus?
Studies published from Colombia and Brazil show the peak risk is when infection occurs during the first trimester or early in the second trimester. That’s consistent with the U.S. registry experience as well. Of note, the median time between development of maternal symptoms and the first notation of fetal microcephaly on ultrasound has been 18 weeks.
“This has important implications for women who’ve been infected. Just because they may have had two consecutive apparently normal monthly fetal ultrasounds doesn’t rule out by any means congenital Zika syndrome because there does appear to be a relatively long time period before these findings appear,” Dr. Honein noted.
What is the full range of potential health problems Zika infection can cause?
“What we’ve seen so far is definitely just the tip of the iceberg,” Dr. Honein cautioned. “It’s very severe, but I think we don’t yet know the full range of disabilities. There’s much more to come here.”
Most of the infants in the U.S. registry are just now reaching 1 year of age. Greater understanding of their neurodevelopment will require follow-up to age 2 or beyond.
Also, the information available to date on Zika-associated birth defects is based largely on scrutiny of infants with microcephaly along with any additional findings, such as chorioretinal scarring.
“We know relatively little about infants with only the other conditions – only hearing loss, for example, or only eye abnormalities,” Dr. Honein said. “While we know there are children who have microcephaly and they have needs, there may be a much larger number of children with lesser impairment, but who still have disabilities that are going to necessitate provision of services. Being prepared for that is very important.”
Reports from multiple countries make it clear that babies exposed to Zika in utero can have a normal-appearing head at birth but then become microcephalic later in their first year. The incidence of this phenomenon hasn’t yet been pinned down.
“We’ve learned in the last year and a-half that microcephaly is a key marker of some of the relevant underlying brain abnormalities, but microcephaly is not where our focus should be,” she said.
How long does Zika virus persist in the body?
The viremia typically lasts for anywhere from a few days up to 2 weeks. However, viral persistence for as long as 107 days has been documented in some pregnant women.
“I hesitate to put a number on it because every new publication has a longer figure,” Dr. Honein said.
It’s not yet known whether viral persistence in a woman infected prior to her pregnancy is associated with adverse fetal outcomes. The central nervous system is clearly a reservoir for persistent virus. Whole blood is now under study as possibly another. Semen poses a major challenge.
“There are case reports of Zika virus RNA being detected in semen for more than 6 months after the timing of infection, but we don’t yet know for how long it can be sexually transmitted. Is there really infectious virus present or just particles of RNA?” she said.
Resources
In partnership with the March of Dimes, the CDC has launched Zika Care Connect, a referral network of roughly 600 specialists in six high-risk states. Their ranks include specialists in maternal-fetal medicine, audiology, radiology, mental health, pediatric neurology, infectious diseases, developmental pediatrics, endocrinology, and pediatric ophthalmology. Another 10 states and at least 600 additional providers will soon be added to the referral network (www.zikacareconnect.org; 1-844-677-0447 toll-free).
Comprehensive, up-to-date Zika information is available to health care providers and the public through the CDC at http://www.cdc.gov/zika, at the Zika Pregnancy Hotline (770-488-7100), and by email at [email protected].
[email protected]
On Twitter @ObGynNews
DENVER – One of many daunting challenges posed by the ongoing global Zika virus epidemic stems from the recent realization that the presence or absence of symptoms in women infected in pregnancy has no bearing on whether their babies will have Zika-associated birth defects, Margaret Honein, PhD, observed at the annual meeting of the Teratology Society.
This has profound clinical consequences because roughly 80% of all maternal Zika infections are asymptomatic or feature such mild symptoms that women don’t report them.
“There was, I think, some hope early on that symptoms in the mother would correlate with outcomes, but that has not been the case at all. In the U.S. population, we’ve seen about a 6% Zika-associated birth defects rate in both symptomatic and asymptomatic mothers,” said Dr. Honein, chief of the birth defects branch at the Centers for Disease Control and Prevention in Atlanta. “We have a huge challenge in identifying the women who have asymptomatic infections, yet they’re at the same risk of having an adverse outcome in their baby.”[[{"fid":"199780","view_mode":"medstat_image_flush_right","fields":
She provided conference attendees with the latest information on Zika, including preliminary results from ongoing CDC investigations. Along the way, she tackled many of the questions Zika experts hear most often from clinicians, while emphasizing that much about congenital Zika syndrome remains unknown.
Just how serious is the global threat of Zika virus infection?
On Feb. 8, 2016, the CDC activated a Level 1 emergency response to Zika. To put that into perspective, this is only the fourth time in history the agency has gone to Level 1. The other occasions were for Hurricane Katrina, the H1N1 pandemic flu, and Ebola.
“This is worse than thalidomide,” said Jan M. Friedman, MD, after listening to Dr. Honein and other speakers at the Zika update held during the conference. Dr. Friedman, a medical geneticist at the University of British Columbia, Vancouver, delivered the Robert L. Brent Lecture.
What is the level of risk for fetal/infant birth defects associated with maternal Zika virus infection?
The birth defect risk is somewhere between 5% and 10%, with the true figure probably being on the high end. Reports quoting risks on the lower end are based upon laboratory testing for maternal IgM antibodies, which couldn’t rule out cross reaction with other flaviviruses, including dengue virus, which is common in most of the same locales as Zika. Women who have been infected with dengue but not Zika are not at increased risk for birth defects. Zika is the first mosquito-borne virus to be recognized as teratogenic in humans.
The birth defects seen in conjunction with Zika infection are not unique. They can have many different causes. CDC investigators examined birth defects data from three states during the year before the Zika outbreak in the Western Hemisphere and determined that the background rate of microcephaly, neural tube defects, eye abnormalities, hearing loss, and other Zika-like birth defects was 3 per 1,000 live births. Among women with Zika virus infection in pregnancy, however, the rate is more than 20-fold higher at 50-100 per 1,000, according to Dr. Honein.
When during pregnancy does maternal Zika infection pose the highest risk to the fetus?
Studies published from Colombia and Brazil show the peak risk is when infection occurs during the first trimester or early in the second trimester. That’s consistent with the U.S. registry experience as well. Of note, the median time between development of maternal symptoms and the first notation of fetal microcephaly on ultrasound has been 18 weeks.
“This has important implications for women who’ve been infected. Just because they may have had two consecutive apparently normal monthly fetal ultrasounds doesn’t rule out by any means congenital Zika syndrome because there does appear to be a relatively long time period before these findings appear,” Dr. Honein noted.
What is the full range of potential health problems Zika infection can cause?
“What we’ve seen so far is definitely just the tip of the iceberg,” Dr. Honein cautioned. “It’s very severe, but I think we don’t yet know the full range of disabilities. There’s much more to come here.”
Most of the infants in the U.S. registry are just now reaching 1 year of age. Greater understanding of their neurodevelopment will require follow-up to age 2 or beyond.
Also, the information available to date on Zika-associated birth defects is based largely on scrutiny of infants with microcephaly along with any additional findings, such as chorioretinal scarring.
“We know relatively little about infants with only the other conditions – only hearing loss, for example, or only eye abnormalities,” Dr. Honein said. “While we know there are children who have microcephaly and they have needs, there may be a much larger number of children with lesser impairment, but who still have disabilities that are going to necessitate provision of services. Being prepared for that is very important.”
Reports from multiple countries make it clear that babies exposed to Zika in utero can have a normal-appearing head at birth but then become microcephalic later in their first year. The incidence of this phenomenon hasn’t yet been pinned down.
“We’ve learned in the last year and a-half that microcephaly is a key marker of some of the relevant underlying brain abnormalities, but microcephaly is not where our focus should be,” she said.
How long does Zika virus persist in the body?
The viremia typically lasts for anywhere from a few days up to 2 weeks. However, viral persistence for as long as 107 days has been documented in some pregnant women.
“I hesitate to put a number on it because every new publication has a longer figure,” Dr. Honein said.
It’s not yet known whether viral persistence in a woman infected prior to her pregnancy is associated with adverse fetal outcomes. The central nervous system is clearly a reservoir for persistent virus. Whole blood is now under study as possibly another. Semen poses a major challenge.
“There are case reports of Zika virus RNA being detected in semen for more than 6 months after the timing of infection, but we don’t yet know for how long it can be sexually transmitted. Is there really infectious virus present or just particles of RNA?” she said.
Resources
In partnership with the March of Dimes, the CDC has launched Zika Care Connect, a referral network of roughly 600 specialists in six high-risk states. Their ranks include specialists in maternal-fetal medicine, audiology, radiology, mental health, pediatric neurology, infectious diseases, developmental pediatrics, endocrinology, and pediatric ophthalmology. Another 10 states and at least 600 additional providers will soon be added to the referral network (www.zikacareconnect.org; 1-844-677-0447 toll-free).
Comprehensive, up-to-date Zika information is available to health care providers and the public through the CDC at http://www.cdc.gov/zika, at the Zika Pregnancy Hotline (770-488-7100), and by email at [email protected].
[email protected]
On Twitter @ObGynNews
DENVER – One of many daunting challenges posed by the ongoing global Zika virus epidemic stems from the recent realization that the presence or absence of symptoms in women infected in pregnancy has no bearing on whether their babies will have Zika-associated birth defects, Margaret Honein, PhD, observed at the annual meeting of the Teratology Society.
This has profound clinical consequences because roughly 80% of all maternal Zika infections are asymptomatic or feature such mild symptoms that women don’t report them.
“There was, I think, some hope early on that symptoms in the mother would correlate with outcomes, but that has not been the case at all. In the U.S. population, we’ve seen about a 6% Zika-associated birth defects rate in both symptomatic and asymptomatic mothers,” said Dr. Honein, chief of the birth defects branch at the Centers for Disease Control and Prevention in Atlanta. “We have a huge challenge in identifying the women who have asymptomatic infections, yet they’re at the same risk of having an adverse outcome in their baby.”[[{"fid":"199780","view_mode":"medstat_image_flush_right","fields":
She provided conference attendees with the latest information on Zika, including preliminary results from ongoing CDC investigations. Along the way, she tackled many of the questions Zika experts hear most often from clinicians, while emphasizing that much about congenital Zika syndrome remains unknown.
Just how serious is the global threat of Zika virus infection?
On Feb. 8, 2016, the CDC activated a Level 1 emergency response to Zika. To put that into perspective, this is only the fourth time in history the agency has gone to Level 1. The other occasions were for Hurricane Katrina, the H1N1 pandemic flu, and Ebola.
“This is worse than thalidomide,” said Jan M. Friedman, MD, after listening to Dr. Honein and other speakers at the Zika update held during the conference. Dr. Friedman, a medical geneticist at the University of British Columbia, Vancouver, delivered the Robert L. Brent Lecture.
What is the level of risk for fetal/infant birth defects associated with maternal Zika virus infection?
The birth defect risk is somewhere between 5% and 10%, with the true figure probably being on the high end. Reports quoting risks on the lower end are based upon laboratory testing for maternal IgM antibodies, which couldn’t rule out cross reaction with other flaviviruses, including dengue virus, which is common in most of the same locales as Zika. Women who have been infected with dengue but not Zika are not at increased risk for birth defects. Zika is the first mosquito-borne virus to be recognized as teratogenic in humans.
The birth defects seen in conjunction with Zika infection are not unique. They can have many different causes. CDC investigators examined birth defects data from three states during the year before the Zika outbreak in the Western Hemisphere and determined that the background rate of microcephaly, neural tube defects, eye abnormalities, hearing loss, and other Zika-like birth defects was 3 per 1,000 live births. Among women with Zika virus infection in pregnancy, however, the rate is more than 20-fold higher at 50-100 per 1,000, according to Dr. Honein.
When during pregnancy does maternal Zika infection pose the highest risk to the fetus?
Studies published from Colombia and Brazil show the peak risk is when infection occurs during the first trimester or early in the second trimester. That’s consistent with the U.S. registry experience as well. Of note, the median time between development of maternal symptoms and the first notation of fetal microcephaly on ultrasound has been 18 weeks.
“This has important implications for women who’ve been infected. Just because they may have had two consecutive apparently normal monthly fetal ultrasounds doesn’t rule out by any means congenital Zika syndrome because there does appear to be a relatively long time period before these findings appear,” Dr. Honein noted.
What is the full range of potential health problems Zika infection can cause?
“What we’ve seen so far is definitely just the tip of the iceberg,” Dr. Honein cautioned. “It’s very severe, but I think we don’t yet know the full range of disabilities. There’s much more to come here.”
Most of the infants in the U.S. registry are just now reaching 1 year of age. Greater understanding of their neurodevelopment will require follow-up to age 2 or beyond.
Also, the information available to date on Zika-associated birth defects is based largely on scrutiny of infants with microcephaly along with any additional findings, such as chorioretinal scarring.
“We know relatively little about infants with only the other conditions – only hearing loss, for example, or only eye abnormalities,” Dr. Honein said. “While we know there are children who have microcephaly and they have needs, there may be a much larger number of children with lesser impairment, but who still have disabilities that are going to necessitate provision of services. Being prepared for that is very important.”
Reports from multiple countries make it clear that babies exposed to Zika in utero can have a normal-appearing head at birth but then become microcephalic later in their first year. The incidence of this phenomenon hasn’t yet been pinned down.
“We’ve learned in the last year and a-half that microcephaly is a key marker of some of the relevant underlying brain abnormalities, but microcephaly is not where our focus should be,” she said.
How long does Zika virus persist in the body?
The viremia typically lasts for anywhere from a few days up to 2 weeks. However, viral persistence for as long as 107 days has been documented in some pregnant women.
“I hesitate to put a number on it because every new publication has a longer figure,” Dr. Honein said.
It’s not yet known whether viral persistence in a woman infected prior to her pregnancy is associated with adverse fetal outcomes. The central nervous system is clearly a reservoir for persistent virus. Whole blood is now under study as possibly another. Semen poses a major challenge.
“There are case reports of Zika virus RNA being detected in semen for more than 6 months after the timing of infection, but we don’t yet know for how long it can be sexually transmitted. Is there really infectious virus present or just particles of RNA?” she said.
Resources
In partnership with the March of Dimes, the CDC has launched Zika Care Connect, a referral network of roughly 600 specialists in six high-risk states. Their ranks include specialists in maternal-fetal medicine, audiology, radiology, mental health, pediatric neurology, infectious diseases, developmental pediatrics, endocrinology, and pediatric ophthalmology. Another 10 states and at least 600 additional providers will soon be added to the referral network (www.zikacareconnect.org; 1-844-677-0447 toll-free).
Comprehensive, up-to-date Zika information is available to health care providers and the public through the CDC at http://www.cdc.gov/zika, at the Zika Pregnancy Hotline (770-488-7100), and by email at [email protected].
[email protected]
On Twitter @ObGynNews
EXPERT ANALYSIS FROM TERATOLOGY SOCIETY 2017
What is the best approach for managing CIED infections?
The case
A 72-year-old man with ischemic cardiomyopathy and left-ventricular ejection fraction of 15% had an cardioverter-defibrillator implanted five years ago for primary prevention of sudden cardiac death. He was brought to the emergency department by his daughter who noticed erythema and swelling over the generator pocket site. His temperature is 100.1° F. Vital signs are otherwise normal and stable.
What are the best initial and definitive management strategies for this patient?
When should a cardiac implanted electronic device (CIED) infection be suspected?
CIED infections generally present in one of two ways: as a local generator pocket infection or as a systemic illness.1 Around 70% of CIED infections present with findings related to the generator pocket site. Findings in such cases include pain, swelling, erythema, induration, and ulceration. Systemic findings range from vague constitutional symptoms to overt sepsis. It is important to note that systemic signs of infection are only present in the minority of cases. Their absence does not rule out a CIED infection.1,2 As such, hospitalists must maintain a high index of suspicion in order to avoid missing the diagnosis.
Unfortunately, it can be difficult to distinguish between a CIED infection and less severe postimplantation complications such as surgical site infections, superficial pocket site infections, and noninfected hematoma.2
What are the risk factors for CIED infections?
The risk factors for CIED infection fit into three broad categories: procedure, patient, and pathogen.
Procedural factors that increase risk of infection include lack of periprocedural antimicrobial prophylaxis, inexperienced physician operator, multiple revision procedures, hematoma formation at the pocket site, and increased amount of hardware.1
Patient factors center on medical comorbidities, including congestive heart failure, diabetes mellitus, chronic kidney disease, immunosuppression, and ongoing oral anticoagulation.1
The specific pathogen also plays a role in infection risk. In one cohort study of 1,524 patients with CIEDs, patients with Staphylococcus aureus bacteremia ended up having confirmed or suspected CIED infections in 54.6% of cases, compared with just 12.0% of patients who had bacteremia with gram-negative bacilli.3
Which bacteria cause most CIED infections?
The vast majority of CIED infections are caused by gram-positive bacteria.1,4 An Italian study of 1,204 patients with CIED infection reported that pathogens isolated from extracted leads were gram-positive bacteria in 92.5% of infections.4 Staph species are the most common pathogens. Coagulase-negative staphylococcus and Staphylococcus aureus accounted for 69% and 13.8% of all isolates, respectively. Of note, 33% of CoNS isolates and 13% of S. aureus isolates were resistant to oxacillin in that study.4
Which initial diagnostic tests should be performed?
Patients should have two sets of blood cultures drawn from two separate sites, prior to administration of antibiotics.1 Current guidelines recommend against aspiration of a suspected infected pocket site because the sensitivity for identifying the causal pathogen is low while the risk of introducing infection to the generator pocket is substantial.1 In the event of CIED removal, pocket tissue and lead tips should be sent for gram stain and culture.1
Do all patients require a transesophageal echocardiogram?
Guidelines recommend a transesophageal echocardiogram (TEE) if suspicion for CIED infection is high based on positive blood cultures, antibiotic initiation prior to culture collection, ongoing systemic illness, or other suggestive signs.1,2 Positive transthoracic echocardiogram findings (for example, a valve vegetation) do not obviate the need for TEE because of the possibility of other relevant complications (including endocarditis and perivalvular extension) for which TEE has a greater sensitivity.1
What is the approach to antimicrobial therapy?
Since most infections involve staphylococcus species, initial empiric antimicrobial therapy should cover both oxacillin-sensitive and oxacillin-resistant strains. Thus, intravenous vancomycin is an appropriate initial choice.1 Culture and sensitivity results should then guide specific therapy decisions.1 Table 1 provides a summary of strategies for antimicrobial selection and duration.
Should all patients undergo complete device removal?
All patients with CIED infection require complete device removal, even if the infection is suspected to be confined to the generator pocket and blood cultures remain negative.2 Patients with superficial or surgical site infections without CIED infection do not require complete device removal. Rather, those cases can be managed with a 7- to 10-day course of oral antimicrobials.1
After device removal, what is the appropriate timing for installing a new device?
The decision to implant a replacement device is often made with input from infectious disease and cardiac electrophysiology experts. The decision must consider both infection and device-related concerns. Importantly, repeat blood cultures must be negative, and any infection in the pocket site should be controlled prior to installing a new device.2
Should all patients with a CIED receive antimicrobial prophylaxis prior to invasive dental, urologic, or endoscopic procedures?
No. Merely having a CIED is not considered an indication for antimicrobial prophylaxis.2
Back to the case
Two sets of blood cultures are drawn, and vancomycin is started as empiric therapy. The culture results show CoNS species, and antimicrobial resistance testing shows oxacillin-resistance.
TEE shows a vegetation on one of the leads but no vegetation on any of the heart valves. Cardiac electrophysiology is consulted and performs a percutaneous extraction of the entire device (generator and leads). Starting on the day of extraction, the patient undergoes two weeks of intravenous antimicrobial therapy with vancomycin. The patient, his family, and the electrophysiology team discuss the patient’s wishes, indications, and potential burdens related to device replacement.
He ultimately decides to have a replacement device installed. An infectious disease specialist is consulted to help define appropriate timing of the new device installation procedure.
Bottom line
The patient clearly had a CIED infection which required TEE, extraction of his CIED, and prolonged antimicrobial therapy.
Dr. Davisson is a primary care physician at Community Health Network in Indianapolis, Ind. Dr. Lockwood is a hospitalist at the Lexington VA Medical Center. Dr. Sweigart is a hospitalist at the University of Kentucky, Lexington, and the Lexington VA Medical Center.
References
1. Baddour LM, Epstein AE, Erickson CC, et al. Update on Cardiovascular Implantable Electronic Device Infections and Their Management: A Scientific Statement From the American Heart Association. Circulation. 2010;121(3):458-77.
2. Baddour LM, Cha YM, Wilson WR. Infections of Cardiovascular Implantable Electronic Devices. N Engl J Med. 2012;367(9):842-9.
3. Uslan DZ, Sohail MR, St. Sauver JL, et al. Permanent Pacemaker and Implantable Cardioverter Defibrillator Infection: A Population-Based Study. Arch Intern Med. 2007;167(7):669-75.
4. Bongiorni MG, Tascini C, Tagliaferri E, et al. Microbiology of Cardiac Implantable Electronic Device Infections. Europace. 2012;14(9):1334-9.
The case
A 72-year-old man with ischemic cardiomyopathy and left-ventricular ejection fraction of 15% had an cardioverter-defibrillator implanted five years ago for primary prevention of sudden cardiac death. He was brought to the emergency department by his daughter who noticed erythema and swelling over the generator pocket site. His temperature is 100.1° F. Vital signs are otherwise normal and stable.
What are the best initial and definitive management strategies for this patient?
When should a cardiac implanted electronic device (CIED) infection be suspected?
CIED infections generally present in one of two ways: as a local generator pocket infection or as a systemic illness.1 Around 70% of CIED infections present with findings related to the generator pocket site. Findings in such cases include pain, swelling, erythema, induration, and ulceration. Systemic findings range from vague constitutional symptoms to overt sepsis. It is important to note that systemic signs of infection are only present in the minority of cases. Their absence does not rule out a CIED infection.1,2 As such, hospitalists must maintain a high index of suspicion in order to avoid missing the diagnosis.
Unfortunately, it can be difficult to distinguish between a CIED infection and less severe postimplantation complications such as surgical site infections, superficial pocket site infections, and noninfected hematoma.2
What are the risk factors for CIED infections?
The risk factors for CIED infection fit into three broad categories: procedure, patient, and pathogen.
Procedural factors that increase risk of infection include lack of periprocedural antimicrobial prophylaxis, inexperienced physician operator, multiple revision procedures, hematoma formation at the pocket site, and increased amount of hardware.1
Patient factors center on medical comorbidities, including congestive heart failure, diabetes mellitus, chronic kidney disease, immunosuppression, and ongoing oral anticoagulation.1
The specific pathogen also plays a role in infection risk. In one cohort study of 1,524 patients with CIEDs, patients with Staphylococcus aureus bacteremia ended up having confirmed or suspected CIED infections in 54.6% of cases, compared with just 12.0% of patients who had bacteremia with gram-negative bacilli.3
Which bacteria cause most CIED infections?
The vast majority of CIED infections are caused by gram-positive bacteria.1,4 An Italian study of 1,204 patients with CIED infection reported that pathogens isolated from extracted leads were gram-positive bacteria in 92.5% of infections.4 Staph species are the most common pathogens. Coagulase-negative staphylococcus and Staphylococcus aureus accounted for 69% and 13.8% of all isolates, respectively. Of note, 33% of CoNS isolates and 13% of S. aureus isolates were resistant to oxacillin in that study.4
Which initial diagnostic tests should be performed?
Patients should have two sets of blood cultures drawn from two separate sites, prior to administration of antibiotics.1 Current guidelines recommend against aspiration of a suspected infected pocket site because the sensitivity for identifying the causal pathogen is low while the risk of introducing infection to the generator pocket is substantial.1 In the event of CIED removal, pocket tissue and lead tips should be sent for gram stain and culture.1
Do all patients require a transesophageal echocardiogram?
Guidelines recommend a transesophageal echocardiogram (TEE) if suspicion for CIED infection is high based on positive blood cultures, antibiotic initiation prior to culture collection, ongoing systemic illness, or other suggestive signs.1,2 Positive transthoracic echocardiogram findings (for example, a valve vegetation) do not obviate the need for TEE because of the possibility of other relevant complications (including endocarditis and perivalvular extension) for which TEE has a greater sensitivity.1
What is the approach to antimicrobial therapy?
Since most infections involve staphylococcus species, initial empiric antimicrobial therapy should cover both oxacillin-sensitive and oxacillin-resistant strains. Thus, intravenous vancomycin is an appropriate initial choice.1 Culture and sensitivity results should then guide specific therapy decisions.1 Table 1 provides a summary of strategies for antimicrobial selection and duration.
Should all patients undergo complete device removal?
All patients with CIED infection require complete device removal, even if the infection is suspected to be confined to the generator pocket and blood cultures remain negative.2 Patients with superficial or surgical site infections without CIED infection do not require complete device removal. Rather, those cases can be managed with a 7- to 10-day course of oral antimicrobials.1
After device removal, what is the appropriate timing for installing a new device?
The decision to implant a replacement device is often made with input from infectious disease and cardiac electrophysiology experts. The decision must consider both infection and device-related concerns. Importantly, repeat blood cultures must be negative, and any infection in the pocket site should be controlled prior to installing a new device.2
Should all patients with a CIED receive antimicrobial prophylaxis prior to invasive dental, urologic, or endoscopic procedures?
No. Merely having a CIED is not considered an indication for antimicrobial prophylaxis.2
Back to the case
Two sets of blood cultures are drawn, and vancomycin is started as empiric therapy. The culture results show CoNS species, and antimicrobial resistance testing shows oxacillin-resistance.
TEE shows a vegetation on one of the leads but no vegetation on any of the heart valves. Cardiac electrophysiology is consulted and performs a percutaneous extraction of the entire device (generator and leads). Starting on the day of extraction, the patient undergoes two weeks of intravenous antimicrobial therapy with vancomycin. The patient, his family, and the electrophysiology team discuss the patient’s wishes, indications, and potential burdens related to device replacement.
He ultimately decides to have a replacement device installed. An infectious disease specialist is consulted to help define appropriate timing of the new device installation procedure.
Bottom line
The patient clearly had a CIED infection which required TEE, extraction of his CIED, and prolonged antimicrobial therapy.
Dr. Davisson is a primary care physician at Community Health Network in Indianapolis, Ind. Dr. Lockwood is a hospitalist at the Lexington VA Medical Center. Dr. Sweigart is a hospitalist at the University of Kentucky, Lexington, and the Lexington VA Medical Center.
References
1. Baddour LM, Epstein AE, Erickson CC, et al. Update on Cardiovascular Implantable Electronic Device Infections and Their Management: A Scientific Statement From the American Heart Association. Circulation. 2010;121(3):458-77.
2. Baddour LM, Cha YM, Wilson WR. Infections of Cardiovascular Implantable Electronic Devices. N Engl J Med. 2012;367(9):842-9.
3. Uslan DZ, Sohail MR, St. Sauver JL, et al. Permanent Pacemaker and Implantable Cardioverter Defibrillator Infection: A Population-Based Study. Arch Intern Med. 2007;167(7):669-75.
4. Bongiorni MG, Tascini C, Tagliaferri E, et al. Microbiology of Cardiac Implantable Electronic Device Infections. Europace. 2012;14(9):1334-9.
The case
A 72-year-old man with ischemic cardiomyopathy and left-ventricular ejection fraction of 15% had an cardioverter-defibrillator implanted five years ago for primary prevention of sudden cardiac death. He was brought to the emergency department by his daughter who noticed erythema and swelling over the generator pocket site. His temperature is 100.1° F. Vital signs are otherwise normal and stable.
What are the best initial and definitive management strategies for this patient?
When should a cardiac implanted electronic device (CIED) infection be suspected?
CIED infections generally present in one of two ways: as a local generator pocket infection or as a systemic illness.1 Around 70% of CIED infections present with findings related to the generator pocket site. Findings in such cases include pain, swelling, erythema, induration, and ulceration. Systemic findings range from vague constitutional symptoms to overt sepsis. It is important to note that systemic signs of infection are only present in the minority of cases. Their absence does not rule out a CIED infection.1,2 As such, hospitalists must maintain a high index of suspicion in order to avoid missing the diagnosis.
Unfortunately, it can be difficult to distinguish between a CIED infection and less severe postimplantation complications such as surgical site infections, superficial pocket site infections, and noninfected hematoma.2
What are the risk factors for CIED infections?
The risk factors for CIED infection fit into three broad categories: procedure, patient, and pathogen.
Procedural factors that increase risk of infection include lack of periprocedural antimicrobial prophylaxis, inexperienced physician operator, multiple revision procedures, hematoma formation at the pocket site, and increased amount of hardware.1
Patient factors center on medical comorbidities, including congestive heart failure, diabetes mellitus, chronic kidney disease, immunosuppression, and ongoing oral anticoagulation.1
The specific pathogen also plays a role in infection risk. In one cohort study of 1,524 patients with CIEDs, patients with Staphylococcus aureus bacteremia ended up having confirmed or suspected CIED infections in 54.6% of cases, compared with just 12.0% of patients who had bacteremia with gram-negative bacilli.3
Which bacteria cause most CIED infections?
The vast majority of CIED infections are caused by gram-positive bacteria.1,4 An Italian study of 1,204 patients with CIED infection reported that pathogens isolated from extracted leads were gram-positive bacteria in 92.5% of infections.4 Staph species are the most common pathogens. Coagulase-negative staphylococcus and Staphylococcus aureus accounted for 69% and 13.8% of all isolates, respectively. Of note, 33% of CoNS isolates and 13% of S. aureus isolates were resistant to oxacillin in that study.4
Which initial diagnostic tests should be performed?
Patients should have two sets of blood cultures drawn from two separate sites, prior to administration of antibiotics.1 Current guidelines recommend against aspiration of a suspected infected pocket site because the sensitivity for identifying the causal pathogen is low while the risk of introducing infection to the generator pocket is substantial.1 In the event of CIED removal, pocket tissue and lead tips should be sent for gram stain and culture.1
Do all patients require a transesophageal echocardiogram?
Guidelines recommend a transesophageal echocardiogram (TEE) if suspicion for CIED infection is high based on positive blood cultures, antibiotic initiation prior to culture collection, ongoing systemic illness, or other suggestive signs.1,2 Positive transthoracic echocardiogram findings (for example, a valve vegetation) do not obviate the need for TEE because of the possibility of other relevant complications (including endocarditis and perivalvular extension) for which TEE has a greater sensitivity.1
What is the approach to antimicrobial therapy?
Since most infections involve staphylococcus species, initial empiric antimicrobial therapy should cover both oxacillin-sensitive and oxacillin-resistant strains. Thus, intravenous vancomycin is an appropriate initial choice.1 Culture and sensitivity results should then guide specific therapy decisions.1 Table 1 provides a summary of strategies for antimicrobial selection and duration.
Should all patients undergo complete device removal?
All patients with CIED infection require complete device removal, even if the infection is suspected to be confined to the generator pocket and blood cultures remain negative.2 Patients with superficial or surgical site infections without CIED infection do not require complete device removal. Rather, those cases can be managed with a 7- to 10-day course of oral antimicrobials.1
After device removal, what is the appropriate timing for installing a new device?
The decision to implant a replacement device is often made with input from infectious disease and cardiac electrophysiology experts. The decision must consider both infection and device-related concerns. Importantly, repeat blood cultures must be negative, and any infection in the pocket site should be controlled prior to installing a new device.2
Should all patients with a CIED receive antimicrobial prophylaxis prior to invasive dental, urologic, or endoscopic procedures?
No. Merely having a CIED is not considered an indication for antimicrobial prophylaxis.2
Back to the case
Two sets of blood cultures are drawn, and vancomycin is started as empiric therapy. The culture results show CoNS species, and antimicrobial resistance testing shows oxacillin-resistance.
TEE shows a vegetation on one of the leads but no vegetation on any of the heart valves. Cardiac electrophysiology is consulted and performs a percutaneous extraction of the entire device (generator and leads). Starting on the day of extraction, the patient undergoes two weeks of intravenous antimicrobial therapy with vancomycin. The patient, his family, and the electrophysiology team discuss the patient’s wishes, indications, and potential burdens related to device replacement.
He ultimately decides to have a replacement device installed. An infectious disease specialist is consulted to help define appropriate timing of the new device installation procedure.
Bottom line
The patient clearly had a CIED infection which required TEE, extraction of his CIED, and prolonged antimicrobial therapy.
Dr. Davisson is a primary care physician at Community Health Network in Indianapolis, Ind. Dr. Lockwood is a hospitalist at the Lexington VA Medical Center. Dr. Sweigart is a hospitalist at the University of Kentucky, Lexington, and the Lexington VA Medical Center.
References
1. Baddour LM, Epstein AE, Erickson CC, et al. Update on Cardiovascular Implantable Electronic Device Infections and Their Management: A Scientific Statement From the American Heart Association. Circulation. 2010;121(3):458-77.
2. Baddour LM, Cha YM, Wilson WR. Infections of Cardiovascular Implantable Electronic Devices. N Engl J Med. 2012;367(9):842-9.
3. Uslan DZ, Sohail MR, St. Sauver JL, et al. Permanent Pacemaker and Implantable Cardioverter Defibrillator Infection: A Population-Based Study. Arch Intern Med. 2007;167(7):669-75.
4. Bongiorni MG, Tascini C, Tagliaferri E, et al. Microbiology of Cardiac Implantable Electronic Device Infections. Europace. 2012;14(9):1334-9.