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Health costs over 25 times higher for hemophilia B patients than controls
As the burden of hemophilia B in patients increases from mild to severe forms of the disease, the already high economic cost of treatment rises significantly, according to a large retrospective database study.
Researchers developed four profile categories (mild, moderate, moderate-severe, and severe) for men with hemophilia B on the basis of the frequency of hemorrhage events and factor IX replacement claims as identified from the IBM MarketScan database (June 2011–February 2019). The mean annual health care resource use (HRU) and costs were compared between 5,454 patients with hemophilia B and 1:1 demographically matched controls.
Economic burden
Total health care costs rose with increasingly severe clinical profiles, with hemophilia-related treatments being the primary cost driver, researchers led by Tyler W. Buckner, MD, of the University of Colorado at Denver, Aurora, wrote in Blood Advances.
This was particularly true among patients with more severe clinical profiles, who were more likely to be on prophylaxis with all of its associated costs.
The mean overall total costs incurred by patients with hemophilia B over the study period were $201,635 versus $7,879 for matched controls, a more than 25-fold difference (P < .001). In addition, across all four clinical profiles categories, all-cause total costs, medical costs, and pharmacy costs were significantly higher among patients with hemophilia B than matched controls (P < .001 for all), the researchers added.
Annual total health care costs also increased with increasing severity of hemophilia B clinical profiles, ranging from $80,811 and $137,455 in the mild and moderate groups to $251,619 and $632,088 in the moderate-severe and severe groups, respectively.
“Hemophilia-related treatments represented the primary cost driver. HRU was uniformly higher among patients with hemophilia B across clinical profiles, medical service types examined, and with respect to opioid use. The significant burden highlights that unmet needs remain in hemophilia B,” the researchers concluded.
This study was supported by uniQure. Dr. Buckner has received honoraria or fees for serving on advisory boards or as a consultant for uniQure. Several of the coauthors are employees of Analysis Group, which received consulting fees from uniQure to conduct this study, and two of the authors are employees of and own stock in uniQure.
As the burden of hemophilia B in patients increases from mild to severe forms of the disease, the already high economic cost of treatment rises significantly, according to a large retrospective database study.
Researchers developed four profile categories (mild, moderate, moderate-severe, and severe) for men with hemophilia B on the basis of the frequency of hemorrhage events and factor IX replacement claims as identified from the IBM MarketScan database (June 2011–February 2019). The mean annual health care resource use (HRU) and costs were compared between 5,454 patients with hemophilia B and 1:1 demographically matched controls.
Economic burden
Total health care costs rose with increasingly severe clinical profiles, with hemophilia-related treatments being the primary cost driver, researchers led by Tyler W. Buckner, MD, of the University of Colorado at Denver, Aurora, wrote in Blood Advances.
This was particularly true among patients with more severe clinical profiles, who were more likely to be on prophylaxis with all of its associated costs.
The mean overall total costs incurred by patients with hemophilia B over the study period were $201,635 versus $7,879 for matched controls, a more than 25-fold difference (P < .001). In addition, across all four clinical profiles categories, all-cause total costs, medical costs, and pharmacy costs were significantly higher among patients with hemophilia B than matched controls (P < .001 for all), the researchers added.
Annual total health care costs also increased with increasing severity of hemophilia B clinical profiles, ranging from $80,811 and $137,455 in the mild and moderate groups to $251,619 and $632,088 in the moderate-severe and severe groups, respectively.
“Hemophilia-related treatments represented the primary cost driver. HRU was uniformly higher among patients with hemophilia B across clinical profiles, medical service types examined, and with respect to opioid use. The significant burden highlights that unmet needs remain in hemophilia B,” the researchers concluded.
This study was supported by uniQure. Dr. Buckner has received honoraria or fees for serving on advisory boards or as a consultant for uniQure. Several of the coauthors are employees of Analysis Group, which received consulting fees from uniQure to conduct this study, and two of the authors are employees of and own stock in uniQure.
As the burden of hemophilia B in patients increases from mild to severe forms of the disease, the already high economic cost of treatment rises significantly, according to a large retrospective database study.
Researchers developed four profile categories (mild, moderate, moderate-severe, and severe) for men with hemophilia B on the basis of the frequency of hemorrhage events and factor IX replacement claims as identified from the IBM MarketScan database (June 2011–February 2019). The mean annual health care resource use (HRU) and costs were compared between 5,454 patients with hemophilia B and 1:1 demographically matched controls.
Economic burden
Total health care costs rose with increasingly severe clinical profiles, with hemophilia-related treatments being the primary cost driver, researchers led by Tyler W. Buckner, MD, of the University of Colorado at Denver, Aurora, wrote in Blood Advances.
This was particularly true among patients with more severe clinical profiles, who were more likely to be on prophylaxis with all of its associated costs.
The mean overall total costs incurred by patients with hemophilia B over the study period were $201,635 versus $7,879 for matched controls, a more than 25-fold difference (P < .001). In addition, across all four clinical profiles categories, all-cause total costs, medical costs, and pharmacy costs were significantly higher among patients with hemophilia B than matched controls (P < .001 for all), the researchers added.
Annual total health care costs also increased with increasing severity of hemophilia B clinical profiles, ranging from $80,811 and $137,455 in the mild and moderate groups to $251,619 and $632,088 in the moderate-severe and severe groups, respectively.
“Hemophilia-related treatments represented the primary cost driver. HRU was uniformly higher among patients with hemophilia B across clinical profiles, medical service types examined, and with respect to opioid use. The significant burden highlights that unmet needs remain in hemophilia B,” the researchers concluded.
This study was supported by uniQure. Dr. Buckner has received honoraria or fees for serving on advisory boards or as a consultant for uniQure. Several of the coauthors are employees of Analysis Group, which received consulting fees from uniQure to conduct this study, and two of the authors are employees of and own stock in uniQure.
FROM BLOOD ADVANCES
‘Malicious peer review’ destroyed doc’s career, he says
Cardiothoracic surgeon J. Marvin Smith III, MD, had always thrived on a busy practice schedule, often performing 20-30 surgeries a week. A practicing surgeon for more than 40 years, Dr. Smith said he had no plans to slow down anytime soon.
But Dr. Smith said his career was derailed when leaders at Methodist Healthcare System of San Antonio initiated a sudden peer review proceeding against him. The hospital system alleged certain surgeries performed by Dr. Smith had excessive mortality rates. When he proved the data inaccurate, Dr. Smith said administrators next claimed he was cognitively impaired and wasn’t safe to practice.
Dr. Smith has now been embroiled in a peer review dispute with the hospital system for more than 2 years and says the conflict has essentially forced him out of surgical practice. He believes the peer review was “malicious” and was really launched because of complaints he made about nurse staffing and other issues at the hospital.
“I think it is absolutely in bad faith and is disingenuous what they’ve told me along the way,” said Dr. Smith, 73. “It’s because I pointed out deficiencies in nursing care, and they want to get rid of me. It would be a lot easier for them if I had a contract and they could control me better. But the fact that I was independent, meant they had to resort to a malicious peer review to try and push me out.”
Dr. Smith had a peer review hearing with Methodist in March 2021, and in April, a panel found in Dr. Smith’s favor, according to Dr. Smith. The findings were sent to the hospital’s medical board for review, which issued a decision in early May.
Eric A. Pullen, an attorney for Dr. Smith, said he could not go into detail about the board’s decision for legal reasons, but that “the medical board’s decision did not completely resolve the matter, and Dr. Smith intends to exercise his procedural rights, which could include an appeal.”
Methodist Hospital Texsan and its parent company, Methodist Health System of San Antonio, did not respond to messages seeking comment about the case. Without hearing from the hospital system, its side is unknown and it is unclear if there is more to the story from Methodist’s view.
The problem is not new, but some experts, such as Lawrence Huntoon, MD, PhD, say the practice has become more common in recent years, particularly against independent doctors.
Dr. Huntoon believes there is a nationwide trend at many hospitals to get rid of independent physicians and replace them with employed doctors, he said.
However, because most sham peer reviews go on behind closed doors, there are no data to pinpoint its prevalence or measure its growth.
“Independent physicians are basically being purged from medical staffs across the United States,” said Dr. Huntoon, who is chair of the Association of American Physicians and Surgeons’ Committee to Combat Sham Peer Review. “The hospitals want more control over how physicians practice and who they refer to, and they do that by having employees.”
Anthony P. Weiss, MD, MBA, chief medical officer for Beth Israel Deaconess Medical Center said it has not been his experience that independent physicians are being targeted in such a way. Dr. Weiss responded to an inquiry sent to the American Hospital Association for this story.
“As the authority for peer review rests with the organized medical staff (i.e., physicians), and not formally with the hospital per se, the peer review lever is not typically available as a management tool for hospital administration,” said Dr. Weiss, who is a former member of the AHA’s Committee on Clinical Leadership, but who was speaking on behalf of himself.
A spokesman for the AHA said the organization stands behinds Dr. Weiss’ comments.
Peer review remains a foundational aspect of overseeing the safety and appropriateness of healthcare provided by physicians, Dr. Weiss said. Peer review likely varies from hospital to hospital, he added, although the Healthcare Quality Improvement Act provides some level of guidance as does the American Medical Association Code of Medical Ethics (section 9.4.1).
“In essence, both require that the evaluation be conducted in good faith with the intention to improve care, by physicians with adequate training and knowledge, using a process that is fair and inclusive of the physician under review,” he said. “I believe that most medical staffs abide by these ethical principles, but we have little data to confirm this supposition.”
Did hospital target doc for being vocal?
When members of Methodist’s medical staff first approached Dr. Smith with concerns about his surgery outcomes in November 2018, the physician says he was surprised, but that he was open to an assessment.
“They came to me and said they thought my numbers were bad, and I said: ‘Well my gosh, I certainly don’t want that to be the case. I need to see what numbers you are talking about,’ ” Dr. Smith recalled. “I’ve been president of the Bexar County Medical Society; I’ve been involved with standards and ethics for the Society of Thoracic Surgeons. Quality health care means a whole lot to me.”
The statistical information provided by hospital administrators indicated that Dr. Smith’s mortality rates for coronary artery surgery in 2018 were “excessive” and that his rates for aortic surgery were “unacceptable,” according to a lawsuit Dr. Smith filed against the hospital system. Dr. Smith, who is double boarded with the American Board of Surgery and the American Board of Thoracic Surgery, said his outcomes had never come into question in the past. Dr. Smith said the timing was suspicious to him, however, considering he had recently raised concerns with the hospital through letters about nursing performance, staffing, and compensation.
A peer review investigation was initiated. In the meantime, Dr. Smith agreed to intensivist consults on his postoperative patients and consults with the hospital’s “Heart Team” on all preoperative cardiac, valve, and aortic cases. A vocal critic of the Heart Team, Dr. Smith had long contended the entity provided no meaningful benefit to his patients in most cases and, rather, increased hospital stays and raised medical expenses. Despite his agreement, Dr. Smith was later asked to voluntarily stop performing surgeries at the hospital.
“I agreed, convinced that we’d get this all settled,” he said.
Another report issued by the hospital in 2019 also indicated elevated mortality rates associated with some of Smith’s surgeries, although the document differed from the first report, according to the lawsuit. Dr. Smith says he was ignored when he pointed out problems with the data, including a lack of appropriate risk stratification in the report, departure from Society of Thoracic Surgeons data rules, and improper inclusion of his cases in the denominator of the ratio when a comparison was made of his outcomes with those hospitalwide. A subsequent report from Methodist in March 2019 indicated Dr. Smith’s surgery outcomes were “within the expected parameters of performance,” according to court documents.
The surgery accusations were dropped, but the peer review proceeding against Dr. Smith wasn’t over. The hospital next requested that Dr. Smith undergo a competency evaluation.
“When they realized the data was bad, they then changed their argument in the peer review proceeding and essentially started to argue that Dr. Smith had some sort of cognitive disability that prevented him from continuing to practice,” said Mr. Pullen. “The way I look at it, when the initial basis for the peer review was proven false, the hospital found something else and some other reason to try to keep Dr. Smith from practicing.”
Thus began a lengthy disagreement about which entity would conduct the evaluation, who would pay, and the type of acceptable assessment. An evaluation by the hospital’s preferred organization resulted in a finding of mild cognitive impairment, Dr. Smith said. He hired his own experts who conducted separate evaluations, finding no impairment and no basis for the former evaluation’s conclusion.
“Literally, the determinant as to whether I was normal or below normal on their test was one point, which was associated with a finding that I didn’t draw a clock correctly,” Dr. Smith claimed. “The reviewer said my minute hand was a little too short and docked me a point. It was purely subjective. To me, the gold standard of whether you are learned in thoracic surgery is the American Board of Thoracic Surgery’s test. The board’s test shows my cognitive ability is entirely in keeping with my practice. That contrasts with the one point off I got for drawing a clock wrong in somebody’s estimation.”
Conflict leads to legal case
In September 2020, Dr. Smith filed a lawsuit against Methodist Healthcare System of San Antonio, alleging business disparagement by Methodist for allegedly publishing false and disparaging information about Dr. Smith and tortious interference with business relations. The latter claim stems from Methodist refusing to provide documents to other hospitals about the status of Dr. Smith’s privileges at Methodist, Mr. Pullen said.
Because Methodist refused to confirm his status, the renewal process for Baptist Health System could not be completed and Dr. Smith lost his privileges at Baptist Health System facilities, according to the lawsuit.
Notably, Dr. Smith’s legal challenge also asks the court to take a stance against alleged amendments by Methodist to its Unified Medical Staff Bylaws. The hospital allegedly proposed changes that would prevent physicians from seeking legal action against the hospital for malicious peer review, according to Dr. Smith’s lawsuit.
The amendments would make the peer review process itself the “sole and exclusive remedy with respect to any action or recommendation taken at the hospital affecting medical staff appointment and/or clinical privileges,” according to an excerpt of the proposed amendments included in Dr. Smith’s lawsuit. In addition, the changes would hold practitioners liable for lost revenues if the doctor initiates “any type of legal action challenging credentialing, privileging, or other medical peer review or professional review activity,” according to the lawsuit.
Dr. Smith’s lawsuit seeks a declaration that the proposed amendments to the bylaws are “void as against public policy,” and a declaration that the proposed amendments to the bylaws cannot take away physicians’ statutory right to bring litigation against Methodist for malicious peer review.
“The proposed amendments have a tendency to and will injure the public good,” Dr. Smith argued in the lawsuit. “The proposed amendments allow Methodist to act with malice and in bad faith in conducting peer review proceedings and face no legal repercussions.”
Regardless of the final outcome of the peer review proceeding, Mr. Pullen said the harm Dr. Smith has already endured cannot be reversed.
“Even if comes out in his favor, the damage is already done,” he said. “It will not remedy the damage Dr. Smith has incurred.”
Fighting sham peer review is difficult
Battling a malicious peer review has long been an uphill battle for physicians, according to Dr. Huntoon. That’s because the Health Care Quality Improvement Act (HCQIA), a federal law passed in 1986, provides near absolute immunity to hospitals and peer reviewers in legal disputes.
The HCQIA was created by Congress to extend immunity to good-faith peer review of doctors and to increase overall participation in peer review by removing fear of litigation. However, the act has also enabled abuse of peer review by shielding bad-faith reviewers from accountability, said Dr. Huntoon.
“The Health Care Quality Improvement Act presumes that what the hospital did was warranted and reasonable and shifts the burden to the physician to prove his innocence by a preponderance of evidence,” he said. “That’s an entirely foreign concept to most people who think a person should be considered innocent until proven guilty. Here, it’s the exact opposite.”
The HCQIA has been challenged numerous times over the years and tested at the appellate level, but continues to survive and remain settled law, added Richard B. Willner, DPM, founder and director of the Center for Peer Review Justice, which assists and counsels physicians about sham peer review.
In 2011, former Rep. Joe Heck, DO, (R-Nev.) introduced a bill that would have amended the HCQIA to prohibit a professional review entity from submitting a report to the National Practitioner Data Bank (NPDB) while the doctor was still under investigation and before the doctor was afforded adequate notice and a hearing. Although the measure had 16 cosponsors and plenty of support from the physician community, it failed.
In addition to a heavy legal burden, physicians who experience malicious peer reviews also face ramifications from being reported to the NPDB. Peer review organizations are required to report certain negative actions or findings to the NPDB.
“A databank entry is a scarlet letter on your forehead,” Dr. Willner said. “The rules at a lot of institutions are not to take anyone who has been databanked, rightfully or wrongfully. And what is the evidence necessary to databank you? None. There’s no evidence needed to databank somebody.”
Despite the bleak landscape, experts say progress has been made on a case-by-case basis by physicians who have succeeded in fighting back against questionable peer reviews in recent years.
In January 2020, Indiana ob.gyn. Rebecca Denman, MD, prevailed in her defamation lawsuit against St Vincent Carmel Hospital and St Vincent Carmel Medical Group, winning $4.75 million in damages. Dr. Denman alleged administrators failed to conduct a proper peer review investigation after a false allegation by a nurse that she was under the influence while on the job.
Indianapolis attorney Kathleen A. DeLaney, who represented Dr. Denman, said hospital leaders misled Dr. Denman into believing a peer review had occurred when no formal peer review hearing or proceeding took place.
“The CMO of the medical group claimed that he performed a peer review ‘screening,’ but he never informed the other members of the peer review executive committee of the matter until after he had placed Dr. Denman on administrative leave,” Ms. DeLaney said. “He also neglected to tell the peer review executive committee that the substance abuse policy had not been followed, or that Dr. Denman had not been tested for alcohol use – due to the 12-hour delay in report.”
Dr. Denman was ultimately required to undergo an alcohol abuse evaluation, enter a treatment program, and sign a 5-year monitoring contract with the Indiana State Medical Association as a condition of her employment, according to the lawsuit. She claimed repercussions from the false allegation resulted in lost compensation, out-of-pocket expenses, emotional distress, and damage to her professional reputation.
She sued the hospital in July 2018, alleging fraud, defamation, tortious interference with an employment relationship, and negligent misrepresentation. After a 4-day trial, jurors found in her favor, awarding Dr. Denman $2 million for her defamation claims, $2 million for her claims of fraud and constructive fraud, $500,000 for her claim of tortious interference with an employment relationship, and $250,000 for her claim of negligent misrepresentation.
A hospital spokesperson said Ascension St Vincent is pursuing an appeal, and that it looks “forward to the opportunity to bring this matter before the Indiana Court of Appeals in June.”
In another case, South Dakota surgeon Linda Miller, MD, was awarded $1.1 million in 2017 after a federal jury found Huron Regional Medical Center breached her contract and violated her due process rights. Dr. Miller became the subject of a peer review at Huron Regional Medical Center when the hospital began analyzing some of her surgery outcomes.
Ken Barker, an attorney for Dr. Miller, said he feels it became evident at trial that the campaign to force Dr. Miller to either resign or lose her privileges was led by the lay board of directors of the hospital and upper-level administration at the hospital.
“They began the process by ordering an unprecedented 90-day review of her medical charts, looking for errors in the medical care she provided patients,” he said. “They could find nothing, so they did a second 90-day review, waiting for a patient’s ‘bad outcome.’ As any general surgeon will say, a ‘bad outcome’ is inevitable. And so it was. Upon that occurrence, they had a medical review committee review the patient’s chart and use it as an excuse to force her to reduce her privileges. Unbeknown to Dr. Miller, an external review had been conducted on another patient’s chart, in which the external review found her care above the standards and, in some measure, ‘exemplary.’ ”
Dr. Miller was eventually pressured to resign, according to her claim. Because of reports made to the NPDB by the medical center, including a patient complication that was allegedly falsified by the hospital, Dr. Miller said she was unable to find work as a general surgeon and went to work as a wound care doctor. At trial, jurors awarded Dr. Miller $586,617 in lost wages, $343,640 for lost future earning capacity, and $250,000 for mental anguish. (The mental anguish award was subsequently struck by a district court.)
Attorneys for Huron Regional Medical Center argued the jury improperly awarded damages and requested a new trial, which was denied by an appeals court.
In the end, the evidence came to light and the jury’s verdict spoke loudly that the hospital had taken unfair advantage of Dr. Miller, Mr. Barker said. But he emphasized that such cases often end differently.
“There are a handful of cases in which physicians like Dr. Miller have challenged the system and won,” he said. “In most cases, however, it is a ‘David vs. Goliath’ scenario where the giant prevails.”
What to do if faced with malicious peer review
An important step when doctors encounter a peer review that they believe is malicious is to consult with an experienced attorney as early as possible, Dr. Huntoon said. “Not all attorneys who set themselves out to be health law attorneys necessarily have knowledge and expertise in sham peer review. And before such a thing happens, I always encourage physicians to read their medical staff bylaws. That’s where everything is set forth, [such as] the corrective action section that tells how peer review is to take place.”
Mr. Barker added that documentation is also key in the event of a potential malicious peer review.
“When a physician senses [the] administration has targeted them, they should start documenting their conversations and actions very carefully, and if possible, recruit another ‘observer’ who can provide a third-party perspective, if necessary,” Mr. Barker said.
Dr. Huntoon recently wrote an article with advice about preparedness and defense of sham peer reviews. The guidance includes that physicians educate themselves about the tactics used by some hospitals to conduct sham peer reviews and the factors that place doctors more at risk. Factors that may raise a doctor’s danger of being targeted include being in solo practice or a small group, being new on staff, or being an older physician approaching retirement as some bad-actor hospitals may view older physicians as being less likely to fight back, said Dr. Huntoon.
Doctors should also keep detailed records and a timeline in the event of a malicious peer review and insist that an independent court reporter record all peer review hearings, even if that means the physician has to pay for the reporter him or herself, according to the guidance. An independent record is invaluable should the physician ultimately issue a future legal challenge against the hospital.
Mr. Willner encourages physicians to call the Center for Peer Review Justice hotline at (504) 621-1670 or visit the website for help with peer review and NPDB issues.
As for Dr. Smith, his days are much quieter and slower today, compared with the active practice he was accustomed to for more than half his life. He misses the fast pace, the patients, and the work that always brought him great joy.
“I hope to get back to doing surgeries eventually,” he said. “I graduated medical school in 1972. Practicing surgery has been my whole life and my career. They have taken my identity and my livelihood away from me based on false numbers and false premises. I want it back.”
A version of this article first appeared on Medscape.com.
Cardiothoracic surgeon J. Marvin Smith III, MD, had always thrived on a busy practice schedule, often performing 20-30 surgeries a week. A practicing surgeon for more than 40 years, Dr. Smith said he had no plans to slow down anytime soon.
But Dr. Smith said his career was derailed when leaders at Methodist Healthcare System of San Antonio initiated a sudden peer review proceeding against him. The hospital system alleged certain surgeries performed by Dr. Smith had excessive mortality rates. When he proved the data inaccurate, Dr. Smith said administrators next claimed he was cognitively impaired and wasn’t safe to practice.
Dr. Smith has now been embroiled in a peer review dispute with the hospital system for more than 2 years and says the conflict has essentially forced him out of surgical practice. He believes the peer review was “malicious” and was really launched because of complaints he made about nurse staffing and other issues at the hospital.
“I think it is absolutely in bad faith and is disingenuous what they’ve told me along the way,” said Dr. Smith, 73. “It’s because I pointed out deficiencies in nursing care, and they want to get rid of me. It would be a lot easier for them if I had a contract and they could control me better. But the fact that I was independent, meant they had to resort to a malicious peer review to try and push me out.”
Dr. Smith had a peer review hearing with Methodist in March 2021, and in April, a panel found in Dr. Smith’s favor, according to Dr. Smith. The findings were sent to the hospital’s medical board for review, which issued a decision in early May.
Eric A. Pullen, an attorney for Dr. Smith, said he could not go into detail about the board’s decision for legal reasons, but that “the medical board’s decision did not completely resolve the matter, and Dr. Smith intends to exercise his procedural rights, which could include an appeal.”
Methodist Hospital Texsan and its parent company, Methodist Health System of San Antonio, did not respond to messages seeking comment about the case. Without hearing from the hospital system, its side is unknown and it is unclear if there is more to the story from Methodist’s view.
The problem is not new, but some experts, such as Lawrence Huntoon, MD, PhD, say the practice has become more common in recent years, particularly against independent doctors.
Dr. Huntoon believes there is a nationwide trend at many hospitals to get rid of independent physicians and replace them with employed doctors, he said.
However, because most sham peer reviews go on behind closed doors, there are no data to pinpoint its prevalence or measure its growth.
“Independent physicians are basically being purged from medical staffs across the United States,” said Dr. Huntoon, who is chair of the Association of American Physicians and Surgeons’ Committee to Combat Sham Peer Review. “The hospitals want more control over how physicians practice and who they refer to, and they do that by having employees.”
Anthony P. Weiss, MD, MBA, chief medical officer for Beth Israel Deaconess Medical Center said it has not been his experience that independent physicians are being targeted in such a way. Dr. Weiss responded to an inquiry sent to the American Hospital Association for this story.
“As the authority for peer review rests with the organized medical staff (i.e., physicians), and not formally with the hospital per se, the peer review lever is not typically available as a management tool for hospital administration,” said Dr. Weiss, who is a former member of the AHA’s Committee on Clinical Leadership, but who was speaking on behalf of himself.
A spokesman for the AHA said the organization stands behinds Dr. Weiss’ comments.
Peer review remains a foundational aspect of overseeing the safety and appropriateness of healthcare provided by physicians, Dr. Weiss said. Peer review likely varies from hospital to hospital, he added, although the Healthcare Quality Improvement Act provides some level of guidance as does the American Medical Association Code of Medical Ethics (section 9.4.1).
“In essence, both require that the evaluation be conducted in good faith with the intention to improve care, by physicians with adequate training and knowledge, using a process that is fair and inclusive of the physician under review,” he said. “I believe that most medical staffs abide by these ethical principles, but we have little data to confirm this supposition.”
Did hospital target doc for being vocal?
When members of Methodist’s medical staff first approached Dr. Smith with concerns about his surgery outcomes in November 2018, the physician says he was surprised, but that he was open to an assessment.
“They came to me and said they thought my numbers were bad, and I said: ‘Well my gosh, I certainly don’t want that to be the case. I need to see what numbers you are talking about,’ ” Dr. Smith recalled. “I’ve been president of the Bexar County Medical Society; I’ve been involved with standards and ethics for the Society of Thoracic Surgeons. Quality health care means a whole lot to me.”
The statistical information provided by hospital administrators indicated that Dr. Smith’s mortality rates for coronary artery surgery in 2018 were “excessive” and that his rates for aortic surgery were “unacceptable,” according to a lawsuit Dr. Smith filed against the hospital system. Dr. Smith, who is double boarded with the American Board of Surgery and the American Board of Thoracic Surgery, said his outcomes had never come into question in the past. Dr. Smith said the timing was suspicious to him, however, considering he had recently raised concerns with the hospital through letters about nursing performance, staffing, and compensation.
A peer review investigation was initiated. In the meantime, Dr. Smith agreed to intensivist consults on his postoperative patients and consults with the hospital’s “Heart Team” on all preoperative cardiac, valve, and aortic cases. A vocal critic of the Heart Team, Dr. Smith had long contended the entity provided no meaningful benefit to his patients in most cases and, rather, increased hospital stays and raised medical expenses. Despite his agreement, Dr. Smith was later asked to voluntarily stop performing surgeries at the hospital.
“I agreed, convinced that we’d get this all settled,” he said.
Another report issued by the hospital in 2019 also indicated elevated mortality rates associated with some of Smith’s surgeries, although the document differed from the first report, according to the lawsuit. Dr. Smith says he was ignored when he pointed out problems with the data, including a lack of appropriate risk stratification in the report, departure from Society of Thoracic Surgeons data rules, and improper inclusion of his cases in the denominator of the ratio when a comparison was made of his outcomes with those hospitalwide. A subsequent report from Methodist in March 2019 indicated Dr. Smith’s surgery outcomes were “within the expected parameters of performance,” according to court documents.
The surgery accusations were dropped, but the peer review proceeding against Dr. Smith wasn’t over. The hospital next requested that Dr. Smith undergo a competency evaluation.
“When they realized the data was bad, they then changed their argument in the peer review proceeding and essentially started to argue that Dr. Smith had some sort of cognitive disability that prevented him from continuing to practice,” said Mr. Pullen. “The way I look at it, when the initial basis for the peer review was proven false, the hospital found something else and some other reason to try to keep Dr. Smith from practicing.”
Thus began a lengthy disagreement about which entity would conduct the evaluation, who would pay, and the type of acceptable assessment. An evaluation by the hospital’s preferred organization resulted in a finding of mild cognitive impairment, Dr. Smith said. He hired his own experts who conducted separate evaluations, finding no impairment and no basis for the former evaluation’s conclusion.
“Literally, the determinant as to whether I was normal or below normal on their test was one point, which was associated with a finding that I didn’t draw a clock correctly,” Dr. Smith claimed. “The reviewer said my minute hand was a little too short and docked me a point. It was purely subjective. To me, the gold standard of whether you are learned in thoracic surgery is the American Board of Thoracic Surgery’s test. The board’s test shows my cognitive ability is entirely in keeping with my practice. That contrasts with the one point off I got for drawing a clock wrong in somebody’s estimation.”
Conflict leads to legal case
In September 2020, Dr. Smith filed a lawsuit against Methodist Healthcare System of San Antonio, alleging business disparagement by Methodist for allegedly publishing false and disparaging information about Dr. Smith and tortious interference with business relations. The latter claim stems from Methodist refusing to provide documents to other hospitals about the status of Dr. Smith’s privileges at Methodist, Mr. Pullen said.
Because Methodist refused to confirm his status, the renewal process for Baptist Health System could not be completed and Dr. Smith lost his privileges at Baptist Health System facilities, according to the lawsuit.
Notably, Dr. Smith’s legal challenge also asks the court to take a stance against alleged amendments by Methodist to its Unified Medical Staff Bylaws. The hospital allegedly proposed changes that would prevent physicians from seeking legal action against the hospital for malicious peer review, according to Dr. Smith’s lawsuit.
The amendments would make the peer review process itself the “sole and exclusive remedy with respect to any action or recommendation taken at the hospital affecting medical staff appointment and/or clinical privileges,” according to an excerpt of the proposed amendments included in Dr. Smith’s lawsuit. In addition, the changes would hold practitioners liable for lost revenues if the doctor initiates “any type of legal action challenging credentialing, privileging, or other medical peer review or professional review activity,” according to the lawsuit.
Dr. Smith’s lawsuit seeks a declaration that the proposed amendments to the bylaws are “void as against public policy,” and a declaration that the proposed amendments to the bylaws cannot take away physicians’ statutory right to bring litigation against Methodist for malicious peer review.
“The proposed amendments have a tendency to and will injure the public good,” Dr. Smith argued in the lawsuit. “The proposed amendments allow Methodist to act with malice and in bad faith in conducting peer review proceedings and face no legal repercussions.”
Regardless of the final outcome of the peer review proceeding, Mr. Pullen said the harm Dr. Smith has already endured cannot be reversed.
“Even if comes out in his favor, the damage is already done,” he said. “It will not remedy the damage Dr. Smith has incurred.”
Fighting sham peer review is difficult
Battling a malicious peer review has long been an uphill battle for physicians, according to Dr. Huntoon. That’s because the Health Care Quality Improvement Act (HCQIA), a federal law passed in 1986, provides near absolute immunity to hospitals and peer reviewers in legal disputes.
The HCQIA was created by Congress to extend immunity to good-faith peer review of doctors and to increase overall participation in peer review by removing fear of litigation. However, the act has also enabled abuse of peer review by shielding bad-faith reviewers from accountability, said Dr. Huntoon.
“The Health Care Quality Improvement Act presumes that what the hospital did was warranted and reasonable and shifts the burden to the physician to prove his innocence by a preponderance of evidence,” he said. “That’s an entirely foreign concept to most people who think a person should be considered innocent until proven guilty. Here, it’s the exact opposite.”
The HCQIA has been challenged numerous times over the years and tested at the appellate level, but continues to survive and remain settled law, added Richard B. Willner, DPM, founder and director of the Center for Peer Review Justice, which assists and counsels physicians about sham peer review.
In 2011, former Rep. Joe Heck, DO, (R-Nev.) introduced a bill that would have amended the HCQIA to prohibit a professional review entity from submitting a report to the National Practitioner Data Bank (NPDB) while the doctor was still under investigation and before the doctor was afforded adequate notice and a hearing. Although the measure had 16 cosponsors and plenty of support from the physician community, it failed.
In addition to a heavy legal burden, physicians who experience malicious peer reviews also face ramifications from being reported to the NPDB. Peer review organizations are required to report certain negative actions or findings to the NPDB.
“A databank entry is a scarlet letter on your forehead,” Dr. Willner said. “The rules at a lot of institutions are not to take anyone who has been databanked, rightfully or wrongfully. And what is the evidence necessary to databank you? None. There’s no evidence needed to databank somebody.”
Despite the bleak landscape, experts say progress has been made on a case-by-case basis by physicians who have succeeded in fighting back against questionable peer reviews in recent years.
In January 2020, Indiana ob.gyn. Rebecca Denman, MD, prevailed in her defamation lawsuit against St Vincent Carmel Hospital and St Vincent Carmel Medical Group, winning $4.75 million in damages. Dr. Denman alleged administrators failed to conduct a proper peer review investigation after a false allegation by a nurse that she was under the influence while on the job.
Indianapolis attorney Kathleen A. DeLaney, who represented Dr. Denman, said hospital leaders misled Dr. Denman into believing a peer review had occurred when no formal peer review hearing or proceeding took place.
“The CMO of the medical group claimed that he performed a peer review ‘screening,’ but he never informed the other members of the peer review executive committee of the matter until after he had placed Dr. Denman on administrative leave,” Ms. DeLaney said. “He also neglected to tell the peer review executive committee that the substance abuse policy had not been followed, or that Dr. Denman had not been tested for alcohol use – due to the 12-hour delay in report.”
Dr. Denman was ultimately required to undergo an alcohol abuse evaluation, enter a treatment program, and sign a 5-year monitoring contract with the Indiana State Medical Association as a condition of her employment, according to the lawsuit. She claimed repercussions from the false allegation resulted in lost compensation, out-of-pocket expenses, emotional distress, and damage to her professional reputation.
She sued the hospital in July 2018, alleging fraud, defamation, tortious interference with an employment relationship, and negligent misrepresentation. After a 4-day trial, jurors found in her favor, awarding Dr. Denman $2 million for her defamation claims, $2 million for her claims of fraud and constructive fraud, $500,000 for her claim of tortious interference with an employment relationship, and $250,000 for her claim of negligent misrepresentation.
A hospital spokesperson said Ascension St Vincent is pursuing an appeal, and that it looks “forward to the opportunity to bring this matter before the Indiana Court of Appeals in June.”
In another case, South Dakota surgeon Linda Miller, MD, was awarded $1.1 million in 2017 after a federal jury found Huron Regional Medical Center breached her contract and violated her due process rights. Dr. Miller became the subject of a peer review at Huron Regional Medical Center when the hospital began analyzing some of her surgery outcomes.
Ken Barker, an attorney for Dr. Miller, said he feels it became evident at trial that the campaign to force Dr. Miller to either resign or lose her privileges was led by the lay board of directors of the hospital and upper-level administration at the hospital.
“They began the process by ordering an unprecedented 90-day review of her medical charts, looking for errors in the medical care she provided patients,” he said. “They could find nothing, so they did a second 90-day review, waiting for a patient’s ‘bad outcome.’ As any general surgeon will say, a ‘bad outcome’ is inevitable. And so it was. Upon that occurrence, they had a medical review committee review the patient’s chart and use it as an excuse to force her to reduce her privileges. Unbeknown to Dr. Miller, an external review had been conducted on another patient’s chart, in which the external review found her care above the standards and, in some measure, ‘exemplary.’ ”
Dr. Miller was eventually pressured to resign, according to her claim. Because of reports made to the NPDB by the medical center, including a patient complication that was allegedly falsified by the hospital, Dr. Miller said she was unable to find work as a general surgeon and went to work as a wound care doctor. At trial, jurors awarded Dr. Miller $586,617 in lost wages, $343,640 for lost future earning capacity, and $250,000 for mental anguish. (The mental anguish award was subsequently struck by a district court.)
Attorneys for Huron Regional Medical Center argued the jury improperly awarded damages and requested a new trial, which was denied by an appeals court.
In the end, the evidence came to light and the jury’s verdict spoke loudly that the hospital had taken unfair advantage of Dr. Miller, Mr. Barker said. But he emphasized that such cases often end differently.
“There are a handful of cases in which physicians like Dr. Miller have challenged the system and won,” he said. “In most cases, however, it is a ‘David vs. Goliath’ scenario where the giant prevails.”
What to do if faced with malicious peer review
An important step when doctors encounter a peer review that they believe is malicious is to consult with an experienced attorney as early as possible, Dr. Huntoon said. “Not all attorneys who set themselves out to be health law attorneys necessarily have knowledge and expertise in sham peer review. And before such a thing happens, I always encourage physicians to read their medical staff bylaws. That’s where everything is set forth, [such as] the corrective action section that tells how peer review is to take place.”
Mr. Barker added that documentation is also key in the event of a potential malicious peer review.
“When a physician senses [the] administration has targeted them, they should start documenting their conversations and actions very carefully, and if possible, recruit another ‘observer’ who can provide a third-party perspective, if necessary,” Mr. Barker said.
Dr. Huntoon recently wrote an article with advice about preparedness and defense of sham peer reviews. The guidance includes that physicians educate themselves about the tactics used by some hospitals to conduct sham peer reviews and the factors that place doctors more at risk. Factors that may raise a doctor’s danger of being targeted include being in solo practice or a small group, being new on staff, or being an older physician approaching retirement as some bad-actor hospitals may view older physicians as being less likely to fight back, said Dr. Huntoon.
Doctors should also keep detailed records and a timeline in the event of a malicious peer review and insist that an independent court reporter record all peer review hearings, even if that means the physician has to pay for the reporter him or herself, according to the guidance. An independent record is invaluable should the physician ultimately issue a future legal challenge against the hospital.
Mr. Willner encourages physicians to call the Center for Peer Review Justice hotline at (504) 621-1670 or visit the website for help with peer review and NPDB issues.
As for Dr. Smith, his days are much quieter and slower today, compared with the active practice he was accustomed to for more than half his life. He misses the fast pace, the patients, and the work that always brought him great joy.
“I hope to get back to doing surgeries eventually,” he said. “I graduated medical school in 1972. Practicing surgery has been my whole life and my career. They have taken my identity and my livelihood away from me based on false numbers and false premises. I want it back.”
A version of this article first appeared on Medscape.com.
Cardiothoracic surgeon J. Marvin Smith III, MD, had always thrived on a busy practice schedule, often performing 20-30 surgeries a week. A practicing surgeon for more than 40 years, Dr. Smith said he had no plans to slow down anytime soon.
But Dr. Smith said his career was derailed when leaders at Methodist Healthcare System of San Antonio initiated a sudden peer review proceeding against him. The hospital system alleged certain surgeries performed by Dr. Smith had excessive mortality rates. When he proved the data inaccurate, Dr. Smith said administrators next claimed he was cognitively impaired and wasn’t safe to practice.
Dr. Smith has now been embroiled in a peer review dispute with the hospital system for more than 2 years and says the conflict has essentially forced him out of surgical practice. He believes the peer review was “malicious” and was really launched because of complaints he made about nurse staffing and other issues at the hospital.
“I think it is absolutely in bad faith and is disingenuous what they’ve told me along the way,” said Dr. Smith, 73. “It’s because I pointed out deficiencies in nursing care, and they want to get rid of me. It would be a lot easier for them if I had a contract and they could control me better. But the fact that I was independent, meant they had to resort to a malicious peer review to try and push me out.”
Dr. Smith had a peer review hearing with Methodist in March 2021, and in April, a panel found in Dr. Smith’s favor, according to Dr. Smith. The findings were sent to the hospital’s medical board for review, which issued a decision in early May.
Eric A. Pullen, an attorney for Dr. Smith, said he could not go into detail about the board’s decision for legal reasons, but that “the medical board’s decision did not completely resolve the matter, and Dr. Smith intends to exercise his procedural rights, which could include an appeal.”
Methodist Hospital Texsan and its parent company, Methodist Health System of San Antonio, did not respond to messages seeking comment about the case. Without hearing from the hospital system, its side is unknown and it is unclear if there is more to the story from Methodist’s view.
The problem is not new, but some experts, such as Lawrence Huntoon, MD, PhD, say the practice has become more common in recent years, particularly against independent doctors.
Dr. Huntoon believes there is a nationwide trend at many hospitals to get rid of independent physicians and replace them with employed doctors, he said.
However, because most sham peer reviews go on behind closed doors, there are no data to pinpoint its prevalence or measure its growth.
“Independent physicians are basically being purged from medical staffs across the United States,” said Dr. Huntoon, who is chair of the Association of American Physicians and Surgeons’ Committee to Combat Sham Peer Review. “The hospitals want more control over how physicians practice and who they refer to, and they do that by having employees.”
Anthony P. Weiss, MD, MBA, chief medical officer for Beth Israel Deaconess Medical Center said it has not been his experience that independent physicians are being targeted in such a way. Dr. Weiss responded to an inquiry sent to the American Hospital Association for this story.
“As the authority for peer review rests with the organized medical staff (i.e., physicians), and not formally with the hospital per se, the peer review lever is not typically available as a management tool for hospital administration,” said Dr. Weiss, who is a former member of the AHA’s Committee on Clinical Leadership, but who was speaking on behalf of himself.
A spokesman for the AHA said the organization stands behinds Dr. Weiss’ comments.
Peer review remains a foundational aspect of overseeing the safety and appropriateness of healthcare provided by physicians, Dr. Weiss said. Peer review likely varies from hospital to hospital, he added, although the Healthcare Quality Improvement Act provides some level of guidance as does the American Medical Association Code of Medical Ethics (section 9.4.1).
“In essence, both require that the evaluation be conducted in good faith with the intention to improve care, by physicians with adequate training and knowledge, using a process that is fair and inclusive of the physician under review,” he said. “I believe that most medical staffs abide by these ethical principles, but we have little data to confirm this supposition.”
Did hospital target doc for being vocal?
When members of Methodist’s medical staff first approached Dr. Smith with concerns about his surgery outcomes in November 2018, the physician says he was surprised, but that he was open to an assessment.
“They came to me and said they thought my numbers were bad, and I said: ‘Well my gosh, I certainly don’t want that to be the case. I need to see what numbers you are talking about,’ ” Dr. Smith recalled. “I’ve been president of the Bexar County Medical Society; I’ve been involved with standards and ethics for the Society of Thoracic Surgeons. Quality health care means a whole lot to me.”
The statistical information provided by hospital administrators indicated that Dr. Smith’s mortality rates for coronary artery surgery in 2018 were “excessive” and that his rates for aortic surgery were “unacceptable,” according to a lawsuit Dr. Smith filed against the hospital system. Dr. Smith, who is double boarded with the American Board of Surgery and the American Board of Thoracic Surgery, said his outcomes had never come into question in the past. Dr. Smith said the timing was suspicious to him, however, considering he had recently raised concerns with the hospital through letters about nursing performance, staffing, and compensation.
A peer review investigation was initiated. In the meantime, Dr. Smith agreed to intensivist consults on his postoperative patients and consults with the hospital’s “Heart Team” on all preoperative cardiac, valve, and aortic cases. A vocal critic of the Heart Team, Dr. Smith had long contended the entity provided no meaningful benefit to his patients in most cases and, rather, increased hospital stays and raised medical expenses. Despite his agreement, Dr. Smith was later asked to voluntarily stop performing surgeries at the hospital.
“I agreed, convinced that we’d get this all settled,” he said.
Another report issued by the hospital in 2019 also indicated elevated mortality rates associated with some of Smith’s surgeries, although the document differed from the first report, according to the lawsuit. Dr. Smith says he was ignored when he pointed out problems with the data, including a lack of appropriate risk stratification in the report, departure from Society of Thoracic Surgeons data rules, and improper inclusion of his cases in the denominator of the ratio when a comparison was made of his outcomes with those hospitalwide. A subsequent report from Methodist in March 2019 indicated Dr. Smith’s surgery outcomes were “within the expected parameters of performance,” according to court documents.
The surgery accusations were dropped, but the peer review proceeding against Dr. Smith wasn’t over. The hospital next requested that Dr. Smith undergo a competency evaluation.
“When they realized the data was bad, they then changed their argument in the peer review proceeding and essentially started to argue that Dr. Smith had some sort of cognitive disability that prevented him from continuing to practice,” said Mr. Pullen. “The way I look at it, when the initial basis for the peer review was proven false, the hospital found something else and some other reason to try to keep Dr. Smith from practicing.”
Thus began a lengthy disagreement about which entity would conduct the evaluation, who would pay, and the type of acceptable assessment. An evaluation by the hospital’s preferred organization resulted in a finding of mild cognitive impairment, Dr. Smith said. He hired his own experts who conducted separate evaluations, finding no impairment and no basis for the former evaluation’s conclusion.
“Literally, the determinant as to whether I was normal or below normal on their test was one point, which was associated with a finding that I didn’t draw a clock correctly,” Dr. Smith claimed. “The reviewer said my minute hand was a little too short and docked me a point. It was purely subjective. To me, the gold standard of whether you are learned in thoracic surgery is the American Board of Thoracic Surgery’s test. The board’s test shows my cognitive ability is entirely in keeping with my practice. That contrasts with the one point off I got for drawing a clock wrong in somebody’s estimation.”
Conflict leads to legal case
In September 2020, Dr. Smith filed a lawsuit against Methodist Healthcare System of San Antonio, alleging business disparagement by Methodist for allegedly publishing false and disparaging information about Dr. Smith and tortious interference with business relations. The latter claim stems from Methodist refusing to provide documents to other hospitals about the status of Dr. Smith’s privileges at Methodist, Mr. Pullen said.
Because Methodist refused to confirm his status, the renewal process for Baptist Health System could not be completed and Dr. Smith lost his privileges at Baptist Health System facilities, according to the lawsuit.
Notably, Dr. Smith’s legal challenge also asks the court to take a stance against alleged amendments by Methodist to its Unified Medical Staff Bylaws. The hospital allegedly proposed changes that would prevent physicians from seeking legal action against the hospital for malicious peer review, according to Dr. Smith’s lawsuit.
The amendments would make the peer review process itself the “sole and exclusive remedy with respect to any action or recommendation taken at the hospital affecting medical staff appointment and/or clinical privileges,” according to an excerpt of the proposed amendments included in Dr. Smith’s lawsuit. In addition, the changes would hold practitioners liable for lost revenues if the doctor initiates “any type of legal action challenging credentialing, privileging, or other medical peer review or professional review activity,” according to the lawsuit.
Dr. Smith’s lawsuit seeks a declaration that the proposed amendments to the bylaws are “void as against public policy,” and a declaration that the proposed amendments to the bylaws cannot take away physicians’ statutory right to bring litigation against Methodist for malicious peer review.
“The proposed amendments have a tendency to and will injure the public good,” Dr. Smith argued in the lawsuit. “The proposed amendments allow Methodist to act with malice and in bad faith in conducting peer review proceedings and face no legal repercussions.”
Regardless of the final outcome of the peer review proceeding, Mr. Pullen said the harm Dr. Smith has already endured cannot be reversed.
“Even if comes out in his favor, the damage is already done,” he said. “It will not remedy the damage Dr. Smith has incurred.”
Fighting sham peer review is difficult
Battling a malicious peer review has long been an uphill battle for physicians, according to Dr. Huntoon. That’s because the Health Care Quality Improvement Act (HCQIA), a federal law passed in 1986, provides near absolute immunity to hospitals and peer reviewers in legal disputes.
The HCQIA was created by Congress to extend immunity to good-faith peer review of doctors and to increase overall participation in peer review by removing fear of litigation. However, the act has also enabled abuse of peer review by shielding bad-faith reviewers from accountability, said Dr. Huntoon.
“The Health Care Quality Improvement Act presumes that what the hospital did was warranted and reasonable and shifts the burden to the physician to prove his innocence by a preponderance of evidence,” he said. “That’s an entirely foreign concept to most people who think a person should be considered innocent until proven guilty. Here, it’s the exact opposite.”
The HCQIA has been challenged numerous times over the years and tested at the appellate level, but continues to survive and remain settled law, added Richard B. Willner, DPM, founder and director of the Center for Peer Review Justice, which assists and counsels physicians about sham peer review.
In 2011, former Rep. Joe Heck, DO, (R-Nev.) introduced a bill that would have amended the HCQIA to prohibit a professional review entity from submitting a report to the National Practitioner Data Bank (NPDB) while the doctor was still under investigation and before the doctor was afforded adequate notice and a hearing. Although the measure had 16 cosponsors and plenty of support from the physician community, it failed.
In addition to a heavy legal burden, physicians who experience malicious peer reviews also face ramifications from being reported to the NPDB. Peer review organizations are required to report certain negative actions or findings to the NPDB.
“A databank entry is a scarlet letter on your forehead,” Dr. Willner said. “The rules at a lot of institutions are not to take anyone who has been databanked, rightfully or wrongfully. And what is the evidence necessary to databank you? None. There’s no evidence needed to databank somebody.”
Despite the bleak landscape, experts say progress has been made on a case-by-case basis by physicians who have succeeded in fighting back against questionable peer reviews in recent years.
In January 2020, Indiana ob.gyn. Rebecca Denman, MD, prevailed in her defamation lawsuit against St Vincent Carmel Hospital and St Vincent Carmel Medical Group, winning $4.75 million in damages. Dr. Denman alleged administrators failed to conduct a proper peer review investigation after a false allegation by a nurse that she was under the influence while on the job.
Indianapolis attorney Kathleen A. DeLaney, who represented Dr. Denman, said hospital leaders misled Dr. Denman into believing a peer review had occurred when no formal peer review hearing or proceeding took place.
“The CMO of the medical group claimed that he performed a peer review ‘screening,’ but he never informed the other members of the peer review executive committee of the matter until after he had placed Dr. Denman on administrative leave,” Ms. DeLaney said. “He also neglected to tell the peer review executive committee that the substance abuse policy had not been followed, or that Dr. Denman had not been tested for alcohol use – due to the 12-hour delay in report.”
Dr. Denman was ultimately required to undergo an alcohol abuse evaluation, enter a treatment program, and sign a 5-year monitoring contract with the Indiana State Medical Association as a condition of her employment, according to the lawsuit. She claimed repercussions from the false allegation resulted in lost compensation, out-of-pocket expenses, emotional distress, and damage to her professional reputation.
She sued the hospital in July 2018, alleging fraud, defamation, tortious interference with an employment relationship, and negligent misrepresentation. After a 4-day trial, jurors found in her favor, awarding Dr. Denman $2 million for her defamation claims, $2 million for her claims of fraud and constructive fraud, $500,000 for her claim of tortious interference with an employment relationship, and $250,000 for her claim of negligent misrepresentation.
A hospital spokesperson said Ascension St Vincent is pursuing an appeal, and that it looks “forward to the opportunity to bring this matter before the Indiana Court of Appeals in June.”
In another case, South Dakota surgeon Linda Miller, MD, was awarded $1.1 million in 2017 after a federal jury found Huron Regional Medical Center breached her contract and violated her due process rights. Dr. Miller became the subject of a peer review at Huron Regional Medical Center when the hospital began analyzing some of her surgery outcomes.
Ken Barker, an attorney for Dr. Miller, said he feels it became evident at trial that the campaign to force Dr. Miller to either resign or lose her privileges was led by the lay board of directors of the hospital and upper-level administration at the hospital.
“They began the process by ordering an unprecedented 90-day review of her medical charts, looking for errors in the medical care she provided patients,” he said. “They could find nothing, so they did a second 90-day review, waiting for a patient’s ‘bad outcome.’ As any general surgeon will say, a ‘bad outcome’ is inevitable. And so it was. Upon that occurrence, they had a medical review committee review the patient’s chart and use it as an excuse to force her to reduce her privileges. Unbeknown to Dr. Miller, an external review had been conducted on another patient’s chart, in which the external review found her care above the standards and, in some measure, ‘exemplary.’ ”
Dr. Miller was eventually pressured to resign, according to her claim. Because of reports made to the NPDB by the medical center, including a patient complication that was allegedly falsified by the hospital, Dr. Miller said she was unable to find work as a general surgeon and went to work as a wound care doctor. At trial, jurors awarded Dr. Miller $586,617 in lost wages, $343,640 for lost future earning capacity, and $250,000 for mental anguish. (The mental anguish award was subsequently struck by a district court.)
Attorneys for Huron Regional Medical Center argued the jury improperly awarded damages and requested a new trial, which was denied by an appeals court.
In the end, the evidence came to light and the jury’s verdict spoke loudly that the hospital had taken unfair advantage of Dr. Miller, Mr. Barker said. But he emphasized that such cases often end differently.
“There are a handful of cases in which physicians like Dr. Miller have challenged the system and won,” he said. “In most cases, however, it is a ‘David vs. Goliath’ scenario where the giant prevails.”
What to do if faced with malicious peer review
An important step when doctors encounter a peer review that they believe is malicious is to consult with an experienced attorney as early as possible, Dr. Huntoon said. “Not all attorneys who set themselves out to be health law attorneys necessarily have knowledge and expertise in sham peer review. And before such a thing happens, I always encourage physicians to read their medical staff bylaws. That’s where everything is set forth, [such as] the corrective action section that tells how peer review is to take place.”
Mr. Barker added that documentation is also key in the event of a potential malicious peer review.
“When a physician senses [the] administration has targeted them, they should start documenting their conversations and actions very carefully, and if possible, recruit another ‘observer’ who can provide a third-party perspective, if necessary,” Mr. Barker said.
Dr. Huntoon recently wrote an article with advice about preparedness and defense of sham peer reviews. The guidance includes that physicians educate themselves about the tactics used by some hospitals to conduct sham peer reviews and the factors that place doctors more at risk. Factors that may raise a doctor’s danger of being targeted include being in solo practice or a small group, being new on staff, or being an older physician approaching retirement as some bad-actor hospitals may view older physicians as being less likely to fight back, said Dr. Huntoon.
Doctors should also keep detailed records and a timeline in the event of a malicious peer review and insist that an independent court reporter record all peer review hearings, even if that means the physician has to pay for the reporter him or herself, according to the guidance. An independent record is invaluable should the physician ultimately issue a future legal challenge against the hospital.
Mr. Willner encourages physicians to call the Center for Peer Review Justice hotline at (504) 621-1670 or visit the website for help with peer review and NPDB issues.
As for Dr. Smith, his days are much quieter and slower today, compared with the active practice he was accustomed to for more than half his life. He misses the fast pace, the patients, and the work that always brought him great joy.
“I hope to get back to doing surgeries eventually,” he said. “I graduated medical school in 1972. Practicing surgery has been my whole life and my career. They have taken my identity and my livelihood away from me based on false numbers and false premises. I want it back.”
A version of this article first appeared on Medscape.com.
Dr. Topol talks: COVID-19 variants are innocent until proven guilty
Editor in Chief of this news organization Eric Topol, MD, founder and director of the Scripps Research Translational Institute in La Jolla, Calif., and professor of molecular medicine, has been closely following COVID-19 data since the pandemic began. He spoke with writer Miriam E. Tucker about the latest on SARS-CoV-2 variants and their impact on vaccine efficacy. The conversation serves as a follow-up to his April 13, 2021, New York Times opinion piece, in which he advised readers that “all variants are innocent until proven guilty.”
You have expressed overall confidence in the efficacy of the vaccines thus far despite the emergence of variants, with some caveats. How do you see the current situation?
The Centers for Disease Control and Prevention has designated five “variants of concern,” but only three of them are real concerns – B.1.1.7, first detected in the United Kingdom; P.1, in Brazil and Japan; and B.1.351, in South Africa. Yet, all three are susceptible to our current vaccines.
The U.K. B.1.1.7 is the worst variant of all because it’s hypertransmissible, so I call it a “superspreader strain.” It also causes more severe illness independent of the spread, so it’s a double whammy. It’s clear that it also causes more deaths. The only arguable point is whether it’s 30% or 50% more deaths, but regardless, it’s more lethal and more transmissible.
The B.1.1.7 is going to be the dominant strain worldwide. It could develop new mutations within it that could come back to haunt us. We must keep watch.
But for now, it’s fully responsive to all the vaccines, which is great because if we didn’t have them, we wouldn’t have gotten through this U.S. pandemic like we have, and neither would Israel and the United Kingdom and other countries that have been able to get out of the crisis. We met the enemy and put it in check.
As for the South Africa variant of concern, B.1.351, we just got some encouraging news showing that it›s very responsive to the Pfizer/BioNTech mRNA vaccine in large numbers of people. The study was conducted in Qatar following that country’s mass immunization campaign in which a total of 385,853 people had received at least one vaccine dose and 265,410 had completed the two doses as of March 31, 2021.
At 2 weeks past the second dose, the vaccine was 75% effective at preventing any documented infection with the B.1.351 variant and 89.5% effective against B.1.1.7. The vaccine’s effectiveness against severe, critical, or fatal COVID-19 was greater than 97.4% for all circulating strains in Qatar, where B.1.1.7 and B.1.351 are most prominent.
We also know that B.1.351 is very responsive to the Johnson & Johnson vaccine and the Novavax [vaccine in development] to a lesser degree. It is the most immune-evading variant we’ve seen thus far, with the highest likelihood of providing some vaccine resistance, yet not enough to interfere with vaccination campaigns. So that’s great news.
The caveats here are that you definitely need two doses of the mRNA vaccines to combat the B.1.351 variant. Also, the AstraZeneca vaccine failed to prevent it in South Africa. However, that study was hard to judge because it was underpowered for number of people with mild infections. So, it didn’t look as if it had any efficacy, but maybe it would if tested in a real trial.
The P.1 (Brazil) variant is the second-highest concern after B.1.1.7 because it’s the only one in the United States that’s still headed up. It seems to be competing a bit with B.1.1.7 here. We know it was associated with the crisis in Brazil, in Chile, and some other South American countries. It has some immune escape, but not as bad as B.1.351. It also appears to have somewhat greater transmissibility but not as much as B.1.1.7.
With P.1, we just don’t know enough yet. It was difficult to assess in Brazil because they were in the midst of a catastrophe – like India is now – and you don’t know how much of it is dragged by the catastrophe vs driving it.
We have to respond to P.1 carefully. There are some good data that it does respond to the Chinese vaccine Sinovac and the AstraZeneca vaccine, and it appears to respond to the others as well, based on serum studies. So it doesn’t look like vaccines will be the worry with this variant. Rather, it could be competing with B.1.1.7 and could lead to breakthrough infections in vaccinated people or reinfections in unvaccinated people who had COVID-19. We need several more weeks to sort it out.
Although the B.1.427 and B.1.429 variants initially seen in California remain on the CDC’s concern list, I’m not worried about them.
You mentioned the current COVID-19 crisis in India, where a new variant has been described as a “double mutant,” but on Twitter you called it a “scariant.” Why?
First of all, the B.1.617 variant isn’t a double mutant. It has 15 mutations. It’s a stupid term, focusing on two mutations which largely have been put aside as to concern. One of them is the L452R, which is the same as one of the California variants, and that hasn’t proved to be particularly serious or concerning. The other is the 484Q, and it’s not clear whether that has any function.
The B.1.617 is not the driver of the catastrophe in India. It may be contributing a small amount, but it has been overhyped as the double mutant that’s causing it all. Adding to that are what I call “scariant” headlines here in the United States when a few cases of that variant have been seen.
I coined the term scariant in early February because it was a pretty clear trend. People don’t know what variants are. They know a little bit about mutations but not variants, and they’re scared. A few variants are concerning, but we keep learning more and more things to decrease the concern. That’s why I wrote the New York Times op-ed, to try to provide some reassurance, since there’s such paranoia.
Do you think booster vaccinations will be necessary? If so, will those be of the original vaccines or new ones that incorporate the variants?
As we go forward, there’s still potential for new variants that we haven’t seen yet that combine the worst of all features – transmissibility and immune evasion – especially since we have a world where COVID-19 is unchecked. So, we’re not out of it yet, but at least for the moment, we have vaccines that are capable of protecting against all variants.
In most people, the immune response against SARS-CoV-2 is very durable and strong and may well last for years. With the most closely related SARS-CoV-1, people still had immune responses up to 18 years later. However, some people will have less robust vaccine responses, including the elderly and the immunocompromised. If they don’t have great responses to the vaccine to start with, over time they’re likely to become more vulnerable, especially if they’re exposed to the variants with some degree of immune evasion.
I think we need to study these individuals post vaccination. A lot of people fit into those categories, including seniors, people being treated for cancer or autoimmune conditions, or post organ transplant. We could set up a prospective study to see whether they develop symptomatic COVID-19 and if so, from what – the original strain, B.1.1.7, or the newer variants.
That’s where I think booster shots may be needed. They may not be necessary across the board, but perhaps just in these special subgroups.
All of the current vaccines can be tweaked to include new variants, but the need for that is uncertain as of now. Moderna is working on a so-called bivalent vaccine that includes the original SARS-CoV-2 strain plus the B.1.351 variant, but it isn’t clear that that’s going to be necessary.
Currently, at least 200 COVID-19 vaccines are in development. There will be vaccines you can inhale, room temperature mRNA vaccines, and potentially even oral vaccines.
In the near future, Novavax is close, and there will likely be a two-dose Johnson & Johnson version that has the same potency as the mRNA vaccines. There are a lot of moving parts here.
There may be a step down in efficacy from mRNA to the others, though, and that shouldn’t be discounted. All of the available vaccines so far protect very well against severe disease and death, but some are less effective against mild to moderate infections, which may then lead to long COVID. We don’t yet know whether those who get mild infection post vaccination can still get long COVID.
What do you think it will take to achieve herd immunity?
I prefer the term “containment.” It’s quantitative. If you get to an infection rate of less than 1 in 100,000 people, as they’ve done in Israel, with 0.8 per 100,000, then you have the virus in check, and there will be very little spread when it’s at that controlled rate, with no outbreaks. The United States is currently at about 15 per 100,000. California is at 4. That still has to get lower.
It will be a challenge to get to President Biden’s goal of having 70% of U.S. adults given at least one dose by July 4. We’re now at about 57%. To get that next 13% of adults is going to take an all-out effort: mobile units, going to homes, making it ultraconvenient, education for people with safety concerns, incentivization, and days off.
We also need to get employers, universities, and health systems to get to the mandatory level. We haven’t done that yet. Some universities have mandated it for students, faculty, and staff. We need it in more health care systems. Right now, we only have a couple. We mandate flu shots, and flu is nothing, compared with COVID-19. And the COVID-19 vaccine is far more efficacious – flu shots are 40% efficacious, while these are 95%. COVID-19 is a tenfold more lethal and serious disease, and much more spreadable.
People are using the lack of full licensure by the Food and Drug Administration – as opposed to emergency use authorization – as an excuse not to get vaccinated. A biologics license application takes time to approve. Meanwhile, we have hundreds of millions of doses that have been well tolerated and incredibly effective.
Another aspect to consider regarding containment is that about 110 million Americans have already had COVID-19, even though only about 30 million cases have been confirmed. Most of these people have immune protection, although it’s not as good as if they have one vaccine dose. But they have enough protection to be part of the story here of the wall against COVID-19 and will help us get through this.
That’s a silver lining of having an unchecked epidemic for the entire year of 2020. The good part is that’s helping to get us to achieve an incredible level of containment when we haven’t even been close. Right now, we’re as good as the country has been in the pandemic, but we still have a long gap to get down to that 1 per 100,000. That’s what we should be working toward, and we can get there.
A version of this article first appeared on Medscape.com.
Editor in Chief of this news organization Eric Topol, MD, founder and director of the Scripps Research Translational Institute in La Jolla, Calif., and professor of molecular medicine, has been closely following COVID-19 data since the pandemic began. He spoke with writer Miriam E. Tucker about the latest on SARS-CoV-2 variants and their impact on vaccine efficacy. The conversation serves as a follow-up to his April 13, 2021, New York Times opinion piece, in which he advised readers that “all variants are innocent until proven guilty.”
You have expressed overall confidence in the efficacy of the vaccines thus far despite the emergence of variants, with some caveats. How do you see the current situation?
The Centers for Disease Control and Prevention has designated five “variants of concern,” but only three of them are real concerns – B.1.1.7, first detected in the United Kingdom; P.1, in Brazil and Japan; and B.1.351, in South Africa. Yet, all three are susceptible to our current vaccines.
The U.K. B.1.1.7 is the worst variant of all because it’s hypertransmissible, so I call it a “superspreader strain.” It also causes more severe illness independent of the spread, so it’s a double whammy. It’s clear that it also causes more deaths. The only arguable point is whether it’s 30% or 50% more deaths, but regardless, it’s more lethal and more transmissible.
The B.1.1.7 is going to be the dominant strain worldwide. It could develop new mutations within it that could come back to haunt us. We must keep watch.
But for now, it’s fully responsive to all the vaccines, which is great because if we didn’t have them, we wouldn’t have gotten through this U.S. pandemic like we have, and neither would Israel and the United Kingdom and other countries that have been able to get out of the crisis. We met the enemy and put it in check.
As for the South Africa variant of concern, B.1.351, we just got some encouraging news showing that it›s very responsive to the Pfizer/BioNTech mRNA vaccine in large numbers of people. The study was conducted in Qatar following that country’s mass immunization campaign in which a total of 385,853 people had received at least one vaccine dose and 265,410 had completed the two doses as of March 31, 2021.
At 2 weeks past the second dose, the vaccine was 75% effective at preventing any documented infection with the B.1.351 variant and 89.5% effective against B.1.1.7. The vaccine’s effectiveness against severe, critical, or fatal COVID-19 was greater than 97.4% for all circulating strains in Qatar, where B.1.1.7 and B.1.351 are most prominent.
We also know that B.1.351 is very responsive to the Johnson & Johnson vaccine and the Novavax [vaccine in development] to a lesser degree. It is the most immune-evading variant we’ve seen thus far, with the highest likelihood of providing some vaccine resistance, yet not enough to interfere with vaccination campaigns. So that’s great news.
The caveats here are that you definitely need two doses of the mRNA vaccines to combat the B.1.351 variant. Also, the AstraZeneca vaccine failed to prevent it in South Africa. However, that study was hard to judge because it was underpowered for number of people with mild infections. So, it didn’t look as if it had any efficacy, but maybe it would if tested in a real trial.
The P.1 (Brazil) variant is the second-highest concern after B.1.1.7 because it’s the only one in the United States that’s still headed up. It seems to be competing a bit with B.1.1.7 here. We know it was associated with the crisis in Brazil, in Chile, and some other South American countries. It has some immune escape, but not as bad as B.1.351. It also appears to have somewhat greater transmissibility but not as much as B.1.1.7.
With P.1, we just don’t know enough yet. It was difficult to assess in Brazil because they were in the midst of a catastrophe – like India is now – and you don’t know how much of it is dragged by the catastrophe vs driving it.
We have to respond to P.1 carefully. There are some good data that it does respond to the Chinese vaccine Sinovac and the AstraZeneca vaccine, and it appears to respond to the others as well, based on serum studies. So it doesn’t look like vaccines will be the worry with this variant. Rather, it could be competing with B.1.1.7 and could lead to breakthrough infections in vaccinated people or reinfections in unvaccinated people who had COVID-19. We need several more weeks to sort it out.
Although the B.1.427 and B.1.429 variants initially seen in California remain on the CDC’s concern list, I’m not worried about them.
You mentioned the current COVID-19 crisis in India, where a new variant has been described as a “double mutant,” but on Twitter you called it a “scariant.” Why?
First of all, the B.1.617 variant isn’t a double mutant. It has 15 mutations. It’s a stupid term, focusing on two mutations which largely have been put aside as to concern. One of them is the L452R, which is the same as one of the California variants, and that hasn’t proved to be particularly serious or concerning. The other is the 484Q, and it’s not clear whether that has any function.
The B.1.617 is not the driver of the catastrophe in India. It may be contributing a small amount, but it has been overhyped as the double mutant that’s causing it all. Adding to that are what I call “scariant” headlines here in the United States when a few cases of that variant have been seen.
I coined the term scariant in early February because it was a pretty clear trend. People don’t know what variants are. They know a little bit about mutations but not variants, and they’re scared. A few variants are concerning, but we keep learning more and more things to decrease the concern. That’s why I wrote the New York Times op-ed, to try to provide some reassurance, since there’s such paranoia.
Do you think booster vaccinations will be necessary? If so, will those be of the original vaccines or new ones that incorporate the variants?
As we go forward, there’s still potential for new variants that we haven’t seen yet that combine the worst of all features – transmissibility and immune evasion – especially since we have a world where COVID-19 is unchecked. So, we’re not out of it yet, but at least for the moment, we have vaccines that are capable of protecting against all variants.
In most people, the immune response against SARS-CoV-2 is very durable and strong and may well last for years. With the most closely related SARS-CoV-1, people still had immune responses up to 18 years later. However, some people will have less robust vaccine responses, including the elderly and the immunocompromised. If they don’t have great responses to the vaccine to start with, over time they’re likely to become more vulnerable, especially if they’re exposed to the variants with some degree of immune evasion.
I think we need to study these individuals post vaccination. A lot of people fit into those categories, including seniors, people being treated for cancer or autoimmune conditions, or post organ transplant. We could set up a prospective study to see whether they develop symptomatic COVID-19 and if so, from what – the original strain, B.1.1.7, or the newer variants.
That’s where I think booster shots may be needed. They may not be necessary across the board, but perhaps just in these special subgroups.
All of the current vaccines can be tweaked to include new variants, but the need for that is uncertain as of now. Moderna is working on a so-called bivalent vaccine that includes the original SARS-CoV-2 strain plus the B.1.351 variant, but it isn’t clear that that’s going to be necessary.
Currently, at least 200 COVID-19 vaccines are in development. There will be vaccines you can inhale, room temperature mRNA vaccines, and potentially even oral vaccines.
In the near future, Novavax is close, and there will likely be a two-dose Johnson & Johnson version that has the same potency as the mRNA vaccines. There are a lot of moving parts here.
There may be a step down in efficacy from mRNA to the others, though, and that shouldn’t be discounted. All of the available vaccines so far protect very well against severe disease and death, but some are less effective against mild to moderate infections, which may then lead to long COVID. We don’t yet know whether those who get mild infection post vaccination can still get long COVID.
What do you think it will take to achieve herd immunity?
I prefer the term “containment.” It’s quantitative. If you get to an infection rate of less than 1 in 100,000 people, as they’ve done in Israel, with 0.8 per 100,000, then you have the virus in check, and there will be very little spread when it’s at that controlled rate, with no outbreaks. The United States is currently at about 15 per 100,000. California is at 4. That still has to get lower.
It will be a challenge to get to President Biden’s goal of having 70% of U.S. adults given at least one dose by July 4. We’re now at about 57%. To get that next 13% of adults is going to take an all-out effort: mobile units, going to homes, making it ultraconvenient, education for people with safety concerns, incentivization, and days off.
We also need to get employers, universities, and health systems to get to the mandatory level. We haven’t done that yet. Some universities have mandated it for students, faculty, and staff. We need it in more health care systems. Right now, we only have a couple. We mandate flu shots, and flu is nothing, compared with COVID-19. And the COVID-19 vaccine is far more efficacious – flu shots are 40% efficacious, while these are 95%. COVID-19 is a tenfold more lethal and serious disease, and much more spreadable.
People are using the lack of full licensure by the Food and Drug Administration – as opposed to emergency use authorization – as an excuse not to get vaccinated. A biologics license application takes time to approve. Meanwhile, we have hundreds of millions of doses that have been well tolerated and incredibly effective.
Another aspect to consider regarding containment is that about 110 million Americans have already had COVID-19, even though only about 30 million cases have been confirmed. Most of these people have immune protection, although it’s not as good as if they have one vaccine dose. But they have enough protection to be part of the story here of the wall against COVID-19 and will help us get through this.
That’s a silver lining of having an unchecked epidemic for the entire year of 2020. The good part is that’s helping to get us to achieve an incredible level of containment when we haven’t even been close. Right now, we’re as good as the country has been in the pandemic, but we still have a long gap to get down to that 1 per 100,000. That’s what we should be working toward, and we can get there.
A version of this article first appeared on Medscape.com.
Editor in Chief of this news organization Eric Topol, MD, founder and director of the Scripps Research Translational Institute in La Jolla, Calif., and professor of molecular medicine, has been closely following COVID-19 data since the pandemic began. He spoke with writer Miriam E. Tucker about the latest on SARS-CoV-2 variants and their impact on vaccine efficacy. The conversation serves as a follow-up to his April 13, 2021, New York Times opinion piece, in which he advised readers that “all variants are innocent until proven guilty.”
You have expressed overall confidence in the efficacy of the vaccines thus far despite the emergence of variants, with some caveats. How do you see the current situation?
The Centers for Disease Control and Prevention has designated five “variants of concern,” but only three of them are real concerns – B.1.1.7, first detected in the United Kingdom; P.1, in Brazil and Japan; and B.1.351, in South Africa. Yet, all three are susceptible to our current vaccines.
The U.K. B.1.1.7 is the worst variant of all because it’s hypertransmissible, so I call it a “superspreader strain.” It also causes more severe illness independent of the spread, so it’s a double whammy. It’s clear that it also causes more deaths. The only arguable point is whether it’s 30% or 50% more deaths, but regardless, it’s more lethal and more transmissible.
The B.1.1.7 is going to be the dominant strain worldwide. It could develop new mutations within it that could come back to haunt us. We must keep watch.
But for now, it’s fully responsive to all the vaccines, which is great because if we didn’t have them, we wouldn’t have gotten through this U.S. pandemic like we have, and neither would Israel and the United Kingdom and other countries that have been able to get out of the crisis. We met the enemy and put it in check.
As for the South Africa variant of concern, B.1.351, we just got some encouraging news showing that it›s very responsive to the Pfizer/BioNTech mRNA vaccine in large numbers of people. The study was conducted in Qatar following that country’s mass immunization campaign in which a total of 385,853 people had received at least one vaccine dose and 265,410 had completed the two doses as of March 31, 2021.
At 2 weeks past the second dose, the vaccine was 75% effective at preventing any documented infection with the B.1.351 variant and 89.5% effective against B.1.1.7. The vaccine’s effectiveness against severe, critical, or fatal COVID-19 was greater than 97.4% for all circulating strains in Qatar, where B.1.1.7 and B.1.351 are most prominent.
We also know that B.1.351 is very responsive to the Johnson & Johnson vaccine and the Novavax [vaccine in development] to a lesser degree. It is the most immune-evading variant we’ve seen thus far, with the highest likelihood of providing some vaccine resistance, yet not enough to interfere with vaccination campaigns. So that’s great news.
The caveats here are that you definitely need two doses of the mRNA vaccines to combat the B.1.351 variant. Also, the AstraZeneca vaccine failed to prevent it in South Africa. However, that study was hard to judge because it was underpowered for number of people with mild infections. So, it didn’t look as if it had any efficacy, but maybe it would if tested in a real trial.
The P.1 (Brazil) variant is the second-highest concern after B.1.1.7 because it’s the only one in the United States that’s still headed up. It seems to be competing a bit with B.1.1.7 here. We know it was associated with the crisis in Brazil, in Chile, and some other South American countries. It has some immune escape, but not as bad as B.1.351. It also appears to have somewhat greater transmissibility but not as much as B.1.1.7.
With P.1, we just don’t know enough yet. It was difficult to assess in Brazil because they were in the midst of a catastrophe – like India is now – and you don’t know how much of it is dragged by the catastrophe vs driving it.
We have to respond to P.1 carefully. There are some good data that it does respond to the Chinese vaccine Sinovac and the AstraZeneca vaccine, and it appears to respond to the others as well, based on serum studies. So it doesn’t look like vaccines will be the worry with this variant. Rather, it could be competing with B.1.1.7 and could lead to breakthrough infections in vaccinated people or reinfections in unvaccinated people who had COVID-19. We need several more weeks to sort it out.
Although the B.1.427 and B.1.429 variants initially seen in California remain on the CDC’s concern list, I’m not worried about them.
You mentioned the current COVID-19 crisis in India, where a new variant has been described as a “double mutant,” but on Twitter you called it a “scariant.” Why?
First of all, the B.1.617 variant isn’t a double mutant. It has 15 mutations. It’s a stupid term, focusing on two mutations which largely have been put aside as to concern. One of them is the L452R, which is the same as one of the California variants, and that hasn’t proved to be particularly serious or concerning. The other is the 484Q, and it’s not clear whether that has any function.
The B.1.617 is not the driver of the catastrophe in India. It may be contributing a small amount, but it has been overhyped as the double mutant that’s causing it all. Adding to that are what I call “scariant” headlines here in the United States when a few cases of that variant have been seen.
I coined the term scariant in early February because it was a pretty clear trend. People don’t know what variants are. They know a little bit about mutations but not variants, and they’re scared. A few variants are concerning, but we keep learning more and more things to decrease the concern. That’s why I wrote the New York Times op-ed, to try to provide some reassurance, since there’s such paranoia.
Do you think booster vaccinations will be necessary? If so, will those be of the original vaccines or new ones that incorporate the variants?
As we go forward, there’s still potential for new variants that we haven’t seen yet that combine the worst of all features – transmissibility and immune evasion – especially since we have a world where COVID-19 is unchecked. So, we’re not out of it yet, but at least for the moment, we have vaccines that are capable of protecting against all variants.
In most people, the immune response against SARS-CoV-2 is very durable and strong and may well last for years. With the most closely related SARS-CoV-1, people still had immune responses up to 18 years later. However, some people will have less robust vaccine responses, including the elderly and the immunocompromised. If they don’t have great responses to the vaccine to start with, over time they’re likely to become more vulnerable, especially if they’re exposed to the variants with some degree of immune evasion.
I think we need to study these individuals post vaccination. A lot of people fit into those categories, including seniors, people being treated for cancer or autoimmune conditions, or post organ transplant. We could set up a prospective study to see whether they develop symptomatic COVID-19 and if so, from what – the original strain, B.1.1.7, or the newer variants.
That’s where I think booster shots may be needed. They may not be necessary across the board, but perhaps just in these special subgroups.
All of the current vaccines can be tweaked to include new variants, but the need for that is uncertain as of now. Moderna is working on a so-called bivalent vaccine that includes the original SARS-CoV-2 strain plus the B.1.351 variant, but it isn’t clear that that’s going to be necessary.
Currently, at least 200 COVID-19 vaccines are in development. There will be vaccines you can inhale, room temperature mRNA vaccines, and potentially even oral vaccines.
In the near future, Novavax is close, and there will likely be a two-dose Johnson & Johnson version that has the same potency as the mRNA vaccines. There are a lot of moving parts here.
There may be a step down in efficacy from mRNA to the others, though, and that shouldn’t be discounted. All of the available vaccines so far protect very well against severe disease and death, but some are less effective against mild to moderate infections, which may then lead to long COVID. We don’t yet know whether those who get mild infection post vaccination can still get long COVID.
What do you think it will take to achieve herd immunity?
I prefer the term “containment.” It’s quantitative. If you get to an infection rate of less than 1 in 100,000 people, as they’ve done in Israel, with 0.8 per 100,000, then you have the virus in check, and there will be very little spread when it’s at that controlled rate, with no outbreaks. The United States is currently at about 15 per 100,000. California is at 4. That still has to get lower.
It will be a challenge to get to President Biden’s goal of having 70% of U.S. adults given at least one dose by July 4. We’re now at about 57%. To get that next 13% of adults is going to take an all-out effort: mobile units, going to homes, making it ultraconvenient, education for people with safety concerns, incentivization, and days off.
We also need to get employers, universities, and health systems to get to the mandatory level. We haven’t done that yet. Some universities have mandated it for students, faculty, and staff. We need it in more health care systems. Right now, we only have a couple. We mandate flu shots, and flu is nothing, compared with COVID-19. And the COVID-19 vaccine is far more efficacious – flu shots are 40% efficacious, while these are 95%. COVID-19 is a tenfold more lethal and serious disease, and much more spreadable.
People are using the lack of full licensure by the Food and Drug Administration – as opposed to emergency use authorization – as an excuse not to get vaccinated. A biologics license application takes time to approve. Meanwhile, we have hundreds of millions of doses that have been well tolerated and incredibly effective.
Another aspect to consider regarding containment is that about 110 million Americans have already had COVID-19, even though only about 30 million cases have been confirmed. Most of these people have immune protection, although it’s not as good as if they have one vaccine dose. But they have enough protection to be part of the story here of the wall against COVID-19 and will help us get through this.
That’s a silver lining of having an unchecked epidemic for the entire year of 2020. The good part is that’s helping to get us to achieve an incredible level of containment when we haven’t even been close. Right now, we’re as good as the country has been in the pandemic, but we still have a long gap to get down to that 1 per 100,000. That’s what we should be working toward, and we can get there.
A version of this article first appeared on Medscape.com.
Who can call themselves ‘doctor’? The debate heats up
Who Should Get to Be Called ‘Doctor’? shows. The topic has clearly struck a nerve, since a record number of respondents – over 12,000 – voted in the poll.
Most physicians think it’s appropriate for people with other doctorate degrees such as a PhD or EdD to call themselves ‘doctor,’ although slightly more than half said it depends on the context.
The controversy over who gets to be called a doctor was reignited when a Wall Street Journal opinion piece criticized First Lady Jill Biden, EdD, for wanting to be called “Dr Biden.” The piece also challenged the idea that having a PhD is worth the honorific of ‘doctor.’
Medical ethicist Arthur Caplan, PhD, disagreed with that viewpoint, saying the context matters. For example, he prefers to be called “professor” when he’s introduced to the public rather than “doctor” to avoid any confusion about his professional status.
More than 12,000 clinicians including physicians, medical students, nurses, pharmacists, and other health care professionals responded to the poll. The non-MD clinicians were the most likely to say it was always appropriate to be called “doctor” while physicians were the least likely.
Context matters
Large percentages of clinicians – 54% of doctors, 62% of medical students, and 41% of nurses – said that the context matters for being called “doctor.’’
“I earned my PhD in 1995 and my MD in 2000. I think it is contextual. In a research or University setting, “Dr.” seems appropriate for a PhD. That same person in public should probably not hold themselves out as “Dr.” So, maybe MDs and DOs can choose, while others maintain the title in their specific setting.”
Some readers proposed that people with MDs call themselves physicians rather than doctors. Said one: “Anyone with a terminal doctorate degree has the right to use the word doctor. As a physician when someone asks what I do, I say: ‘I am a physician.’ Problem solved. There can only be one physician but there are many types of doctors.”
Physicians and nurses differed most in their views. Just 24% of physicians said it was always appropriate for people with other doctorate degrees to call themselves doctor whereas about an equal number (22%) thought it was never appropriate.
In contrast, 43% of nurses (including advance practice nurses) said it was always appropriate for people with non-MD doctorates to be called doctor. Only 16% said it’s never appropriate.
This difference may reflect the growing number of nurses with doctorate degrees, either a DNP or PhD, who want to be called doctor in clinical settings.
Age made a difference too. Only 16% of physicians younger than age 45 said it was always appropriate for people with non-MD doctorate degrees to be called doctor, compared with 27% of physicians aged 45 and up.
Medical students (31%) were also more likely than physicians to say it was always appropriate for non-MD doctorates to use the title “doctor” and 64% said it depends on the context. This was noteworthy because twice as many medical students as physicians (16% vs. 8%) said they work in academia, research, or military government settings.
Too many ‘doctors’ confuse the public
Physicians (70%) were also more likely to say it was always or often confusing for the public to hear someone without a medical degree addressed as “doctor.” Only 6% of physicians thought it was never or rarely confusing.
Nurses disagreed. Just 45% said that it was always or often confusing while 16% said it was never or rarely confusing.
Medical students were more aligned with physicians on this issue – 60% said it was always or often confusing to the public and just 10% said it was never or rarely confusing.
One reader commented, “The problem is the confusion the ‘doctor’ title causes for patients, especially in a hospital setting. Is the ‘doctor’ a physician, a pharmacist, a psychologist, a nurse, etc., etc.? We need to think not of our own egos but if and how the confusion about this plethora of titles may be hindering good patient care.”
These concerns are not unfounded. The American Medical Association reported in its Truth in Advertising campaign that “patients mistake physicians with nonphysician providers” based on an online survey of 802 adults in 2018. The participants thought these specialists were MDs: dentists (61%), podiatrists (67%), optometrists (47%), psychologists (43%), doctors of nursing (39%), and chiropractors (27%).
The AMA has advocated that states pass the “Health Care Professional Transparency Act,” which New Jersey has enacted. The law requires all health care professionals dealing with patients to wear a name tag that clearly identifies their licensure. Health care professionals must also display their education, training, and licensure in their office.
A version of this article first appeared on Medscape.com.
Who Should Get to Be Called ‘Doctor’? shows. The topic has clearly struck a nerve, since a record number of respondents – over 12,000 – voted in the poll.
Most physicians think it’s appropriate for people with other doctorate degrees such as a PhD or EdD to call themselves ‘doctor,’ although slightly more than half said it depends on the context.
The controversy over who gets to be called a doctor was reignited when a Wall Street Journal opinion piece criticized First Lady Jill Biden, EdD, for wanting to be called “Dr Biden.” The piece also challenged the idea that having a PhD is worth the honorific of ‘doctor.’
Medical ethicist Arthur Caplan, PhD, disagreed with that viewpoint, saying the context matters. For example, he prefers to be called “professor” when he’s introduced to the public rather than “doctor” to avoid any confusion about his professional status.
More than 12,000 clinicians including physicians, medical students, nurses, pharmacists, and other health care professionals responded to the poll. The non-MD clinicians were the most likely to say it was always appropriate to be called “doctor” while physicians were the least likely.
Context matters
Large percentages of clinicians – 54% of doctors, 62% of medical students, and 41% of nurses – said that the context matters for being called “doctor.’’
“I earned my PhD in 1995 and my MD in 2000. I think it is contextual. In a research or University setting, “Dr.” seems appropriate for a PhD. That same person in public should probably not hold themselves out as “Dr.” So, maybe MDs and DOs can choose, while others maintain the title in their specific setting.”
Some readers proposed that people with MDs call themselves physicians rather than doctors. Said one: “Anyone with a terminal doctorate degree has the right to use the word doctor. As a physician when someone asks what I do, I say: ‘I am a physician.’ Problem solved. There can only be one physician but there are many types of doctors.”
Physicians and nurses differed most in their views. Just 24% of physicians said it was always appropriate for people with other doctorate degrees to call themselves doctor whereas about an equal number (22%) thought it was never appropriate.
In contrast, 43% of nurses (including advance practice nurses) said it was always appropriate for people with non-MD doctorates to be called doctor. Only 16% said it’s never appropriate.
This difference may reflect the growing number of nurses with doctorate degrees, either a DNP or PhD, who want to be called doctor in clinical settings.
Age made a difference too. Only 16% of physicians younger than age 45 said it was always appropriate for people with non-MD doctorate degrees to be called doctor, compared with 27% of physicians aged 45 and up.
Medical students (31%) were also more likely than physicians to say it was always appropriate for non-MD doctorates to use the title “doctor” and 64% said it depends on the context. This was noteworthy because twice as many medical students as physicians (16% vs. 8%) said they work in academia, research, or military government settings.
Too many ‘doctors’ confuse the public
Physicians (70%) were also more likely to say it was always or often confusing for the public to hear someone without a medical degree addressed as “doctor.” Only 6% of physicians thought it was never or rarely confusing.
Nurses disagreed. Just 45% said that it was always or often confusing while 16% said it was never or rarely confusing.
Medical students were more aligned with physicians on this issue – 60% said it was always or often confusing to the public and just 10% said it was never or rarely confusing.
One reader commented, “The problem is the confusion the ‘doctor’ title causes for patients, especially in a hospital setting. Is the ‘doctor’ a physician, a pharmacist, a psychologist, a nurse, etc., etc.? We need to think not of our own egos but if and how the confusion about this plethora of titles may be hindering good patient care.”
These concerns are not unfounded. The American Medical Association reported in its Truth in Advertising campaign that “patients mistake physicians with nonphysician providers” based on an online survey of 802 adults in 2018. The participants thought these specialists were MDs: dentists (61%), podiatrists (67%), optometrists (47%), psychologists (43%), doctors of nursing (39%), and chiropractors (27%).
The AMA has advocated that states pass the “Health Care Professional Transparency Act,” which New Jersey has enacted. The law requires all health care professionals dealing with patients to wear a name tag that clearly identifies their licensure. Health care professionals must also display their education, training, and licensure in their office.
A version of this article first appeared on Medscape.com.
Who Should Get to Be Called ‘Doctor’? shows. The topic has clearly struck a nerve, since a record number of respondents – over 12,000 – voted in the poll.
Most physicians think it’s appropriate for people with other doctorate degrees such as a PhD or EdD to call themselves ‘doctor,’ although slightly more than half said it depends on the context.
The controversy over who gets to be called a doctor was reignited when a Wall Street Journal opinion piece criticized First Lady Jill Biden, EdD, for wanting to be called “Dr Biden.” The piece also challenged the idea that having a PhD is worth the honorific of ‘doctor.’
Medical ethicist Arthur Caplan, PhD, disagreed with that viewpoint, saying the context matters. For example, he prefers to be called “professor” when he’s introduced to the public rather than “doctor” to avoid any confusion about his professional status.
More than 12,000 clinicians including physicians, medical students, nurses, pharmacists, and other health care professionals responded to the poll. The non-MD clinicians were the most likely to say it was always appropriate to be called “doctor” while physicians were the least likely.
Context matters
Large percentages of clinicians – 54% of doctors, 62% of medical students, and 41% of nurses – said that the context matters for being called “doctor.’’
“I earned my PhD in 1995 and my MD in 2000. I think it is contextual. In a research or University setting, “Dr.” seems appropriate for a PhD. That same person in public should probably not hold themselves out as “Dr.” So, maybe MDs and DOs can choose, while others maintain the title in their specific setting.”
Some readers proposed that people with MDs call themselves physicians rather than doctors. Said one: “Anyone with a terminal doctorate degree has the right to use the word doctor. As a physician when someone asks what I do, I say: ‘I am a physician.’ Problem solved. There can only be one physician but there are many types of doctors.”
Physicians and nurses differed most in their views. Just 24% of physicians said it was always appropriate for people with other doctorate degrees to call themselves doctor whereas about an equal number (22%) thought it was never appropriate.
In contrast, 43% of nurses (including advance practice nurses) said it was always appropriate for people with non-MD doctorates to be called doctor. Only 16% said it’s never appropriate.
This difference may reflect the growing number of nurses with doctorate degrees, either a DNP or PhD, who want to be called doctor in clinical settings.
Age made a difference too. Only 16% of physicians younger than age 45 said it was always appropriate for people with non-MD doctorate degrees to be called doctor, compared with 27% of physicians aged 45 and up.
Medical students (31%) were also more likely than physicians to say it was always appropriate for non-MD doctorates to use the title “doctor” and 64% said it depends on the context. This was noteworthy because twice as many medical students as physicians (16% vs. 8%) said they work in academia, research, or military government settings.
Too many ‘doctors’ confuse the public
Physicians (70%) were also more likely to say it was always or often confusing for the public to hear someone without a medical degree addressed as “doctor.” Only 6% of physicians thought it was never or rarely confusing.
Nurses disagreed. Just 45% said that it was always or often confusing while 16% said it was never or rarely confusing.
Medical students were more aligned with physicians on this issue – 60% said it was always or often confusing to the public and just 10% said it was never or rarely confusing.
One reader commented, “The problem is the confusion the ‘doctor’ title causes for patients, especially in a hospital setting. Is the ‘doctor’ a physician, a pharmacist, a psychologist, a nurse, etc., etc.? We need to think not of our own egos but if and how the confusion about this plethora of titles may be hindering good patient care.”
These concerns are not unfounded. The American Medical Association reported in its Truth in Advertising campaign that “patients mistake physicians with nonphysician providers” based on an online survey of 802 adults in 2018. The participants thought these specialists were MDs: dentists (61%), podiatrists (67%), optometrists (47%), psychologists (43%), doctors of nursing (39%), and chiropractors (27%).
The AMA has advocated that states pass the “Health Care Professional Transparency Act,” which New Jersey has enacted. The law requires all health care professionals dealing with patients to wear a name tag that clearly identifies their licensure. Health care professionals must also display their education, training, and licensure in their office.
A version of this article first appeared on Medscape.com.
Moderna announces first data showing efficacy of COVID-19 vaccine booster in development
among people already vaccinated for COVID-19, according to first results released May 5.
Furthermore, data from the company’s ongoing phase 2 study show the variant-specific booster, known as mRNA-1273.351, achieved higher antibody titers against the B.1.351 variant than did a booster with the original Moderna vaccine.
“We are encouraged by these new data, which reinforce our confidence that our booster strategy should be protective against these newly detected variants. The strong and rapid boost in titers to levels above primary vaccination also clearly demonstrates the ability of mRNA-1273 to induce immune memory,” Stéphane Bancel, chief executive officer of Moderna, said in a statement.
The phase 2 study researchers also are evaluating a multivariant booster that is a 50/50 mix of mRNA-1273.351 and mRNA-1273, the initial vaccine given Food and Drug Administration emergency use authorization, in a single vial.
Unlike the two-dose regimen with the original vaccine, the boosters are administered as a single dose immunization.
The trial participants received a booster 6-8 months after primary vaccination. Titers to the wild-type SARS-CoV-2 virus remained high and detectable in 37 out of 40 participants. However, prior to the booster, titers against the two variants of concern, B.1.351 and P.1, were lower, with about half of participants showing undetectable levels.
In contrast, 2 weeks after a booster with the original vaccine or the B.1.351 strain-specific product, pseudovirus neutralizing titers were boosted in all participants and all variants tested.
“Following [the] boost, geometric mean titers against the wild-type, B.1.351, and P.1 variants increased to levels similar to or higher than the previously reported peak titers against the ancestral (D614G) strain following primary vaccination,” the company stated.
Both mRNA-1273.351 and mRNA-1273 booster doses were generally well tolerated, the company reported. Safety and tolerability were generally comparable to those reported after the second dose of the original vaccine. Most adverse events were mild to moderate, with injection site pain most common in both groups. Participants also reported fatigue, headache, myalgia, and arthralgia.
The company plans to release data shortly on the booster efficacy at additional time points beyond 2 weeks for mRNA-1273.351, a lower-dose booster with mRNA-1272/351, as well as data on the multivariant mRNA vaccine booster.
In addition to the company’s phase 2 study, the National Institute of Allergy and Infectious Diseases is conducting a separate phase 1 study of mRNA-1273.351.
A version of this article first appeared on Medscape.com.
among people already vaccinated for COVID-19, according to first results released May 5.
Furthermore, data from the company’s ongoing phase 2 study show the variant-specific booster, known as mRNA-1273.351, achieved higher antibody titers against the B.1.351 variant than did a booster with the original Moderna vaccine.
“We are encouraged by these new data, which reinforce our confidence that our booster strategy should be protective against these newly detected variants. The strong and rapid boost in titers to levels above primary vaccination also clearly demonstrates the ability of mRNA-1273 to induce immune memory,” Stéphane Bancel, chief executive officer of Moderna, said in a statement.
The phase 2 study researchers also are evaluating a multivariant booster that is a 50/50 mix of mRNA-1273.351 and mRNA-1273, the initial vaccine given Food and Drug Administration emergency use authorization, in a single vial.
Unlike the two-dose regimen with the original vaccine, the boosters are administered as a single dose immunization.
The trial participants received a booster 6-8 months after primary vaccination. Titers to the wild-type SARS-CoV-2 virus remained high and detectable in 37 out of 40 participants. However, prior to the booster, titers against the two variants of concern, B.1.351 and P.1, were lower, with about half of participants showing undetectable levels.
In contrast, 2 weeks after a booster with the original vaccine or the B.1.351 strain-specific product, pseudovirus neutralizing titers were boosted in all participants and all variants tested.
“Following [the] boost, geometric mean titers against the wild-type, B.1.351, and P.1 variants increased to levels similar to or higher than the previously reported peak titers against the ancestral (D614G) strain following primary vaccination,” the company stated.
Both mRNA-1273.351 and mRNA-1273 booster doses were generally well tolerated, the company reported. Safety and tolerability were generally comparable to those reported after the second dose of the original vaccine. Most adverse events were mild to moderate, with injection site pain most common in both groups. Participants also reported fatigue, headache, myalgia, and arthralgia.
The company plans to release data shortly on the booster efficacy at additional time points beyond 2 weeks for mRNA-1273.351, a lower-dose booster with mRNA-1272/351, as well as data on the multivariant mRNA vaccine booster.
In addition to the company’s phase 2 study, the National Institute of Allergy and Infectious Diseases is conducting a separate phase 1 study of mRNA-1273.351.
A version of this article first appeared on Medscape.com.
among people already vaccinated for COVID-19, according to first results released May 5.
Furthermore, data from the company’s ongoing phase 2 study show the variant-specific booster, known as mRNA-1273.351, achieved higher antibody titers against the B.1.351 variant than did a booster with the original Moderna vaccine.
“We are encouraged by these new data, which reinforce our confidence that our booster strategy should be protective against these newly detected variants. The strong and rapid boost in titers to levels above primary vaccination also clearly demonstrates the ability of mRNA-1273 to induce immune memory,” Stéphane Bancel, chief executive officer of Moderna, said in a statement.
The phase 2 study researchers also are evaluating a multivariant booster that is a 50/50 mix of mRNA-1273.351 and mRNA-1273, the initial vaccine given Food and Drug Administration emergency use authorization, in a single vial.
Unlike the two-dose regimen with the original vaccine, the boosters are administered as a single dose immunization.
The trial participants received a booster 6-8 months after primary vaccination. Titers to the wild-type SARS-CoV-2 virus remained high and detectable in 37 out of 40 participants. However, prior to the booster, titers against the two variants of concern, B.1.351 and P.1, were lower, with about half of participants showing undetectable levels.
In contrast, 2 weeks after a booster with the original vaccine or the B.1.351 strain-specific product, pseudovirus neutralizing titers were boosted in all participants and all variants tested.
“Following [the] boost, geometric mean titers against the wild-type, B.1.351, and P.1 variants increased to levels similar to or higher than the previously reported peak titers against the ancestral (D614G) strain following primary vaccination,” the company stated.
Both mRNA-1273.351 and mRNA-1273 booster doses were generally well tolerated, the company reported. Safety and tolerability were generally comparable to those reported after the second dose of the original vaccine. Most adverse events were mild to moderate, with injection site pain most common in both groups. Participants also reported fatigue, headache, myalgia, and arthralgia.
The company plans to release data shortly on the booster efficacy at additional time points beyond 2 weeks for mRNA-1273.351, a lower-dose booster with mRNA-1272/351, as well as data on the multivariant mRNA vaccine booster.
In addition to the company’s phase 2 study, the National Institute of Allergy and Infectious Diseases is conducting a separate phase 1 study of mRNA-1273.351.
A version of this article first appeared on Medscape.com.
Prioritize goals of older patients with multimorbidities, gerontologist says
said Mary Tinetti, MD, Gladys Phillips Crofoot Professor of Medicine and Public Health and chief of geriatrics at Yale University, New Haven, Conn.
During a virtual presentation at the American College of Physicians annual Internal Medicine meeting, the gerontologist noted that primary care providers face a number of challenges when managing elderly patients with multimorbidity. These challenges include a lack of representative data in clinical trials, conflicting guideline recommendations, patient nonadherence, and decreased benefit from therapies due to competing conditions, she said.
“Trying to follow multiple guidelines can result in unintentional harms to these people with multiple conditions,” Dr. Tinetti said. She gave examples of the wide-ranging goals patients can have.
“Some [patients] will maximize the focus on function, regardless of how long they are likely to live,” Dr. Tinetti said. “Others will say symptom burden management is most important to them. And others will say they want to live as long as possible, and survival is most important, even if that means a reduction in their function. These individuals also vary in the care they are willing and able to receive to achieve the outcomes that matter most to them.”
For these reasons, Dr. Tinetti recommended patient priorities care, which she and her colleagues have been developing and implementing over the past 5-6 years.
“If the benefits and harms of addressing each condition in isolation is of uncertain benefit and potentially burdensome to both clinician and patient, and we know that patients vary in their health priorities ... then what else would you want to focus on in your 20-minute visit ... except each patient’s priorities?” Dr. Tinetti asked. “This is one solution to the challenge.”
What is patient priorities care?
Patient priorities care is a multidisciplinary, cyclical approach to clinical decision-making composed of three steps, Dr. Tinetti explained. First, a clinician identifies the patient’s health priorities. Second, this information is transmitted to comanaging providers, who decide which of their respective treatments are consistent with the patient’s priorities. And third, those decisions are disseminated to everyone involved in the patient’s care, both within and outside of the health care system, allowing all care providers to align with the patient’s priorities, she noted.
“Each person does that from their own expertise,” Dr. Tinetti said. “The social worker will do something different than the cardiologist, the physical therapist, the endocrinologist – but everybody is aiming at the same outcome – the patient’s priorities.”
In 2019, Dr. Tinetti led a nonrandomized clinical trial to test the feasibility of patient priorities care. The study involved 366 older adults with multimorbidity, among whom 203 received usual care, while 163 received this type of care. Patients in the latter group were twice as likely to have medications stopped, and significantly less likely to have self-management tasks added and diagnostic tests ordered.
How electronic health records can help
In an interview, Dr. Tinetti suggested that comanaging physicians communicate through electronic health records (EHRs), first to ensure that all care providers understand a patient’s goals, then to determine if recommended therapies align with those goals.
“It would be a little bit of a culture change to do that,” Dr. Tinetti said, “but the technology is there and it isn’t too terribly time consuming.”
She went on to suggest that primary care providers are typically best suited to coordinate this process; however, if a patient receives the majority of their care from a particular specialist, then that clinician may be the most suitable coordinator.
Systemic obstacles and solutions
According to Cynthia Boyd, MD, interim director of the division of geriatric medicine and gerontology, Johns Hopkins University, Baltimore, clinicians may encounter obstacles when implementing patient priorities care.
“Our health care system doesn’t always make it easy to do this,” Dr. Boyd said. “It’s important to acknowledge this because it can be hard to do. There’s no question,” Dr. Boyd said in an interview.
Among the headwinds that clinicians may face are clinical practice guidelines, the structure of electronic health records, and quality metrics focused on specific conditions, she explained.
“There’s a lot of things that push us – in primary care and other parts of medicine – away from the approach that’s best for people with multiple chronic conditions,” Dr. Boyd said.
Dr. Tinetti said a challenge to providing this care that she expects is for clinicians, regardless of specialty, “to feel uneasy” about transitioning away from a conventional approach.
Among Dr. Tinetti’s arguments in favor of providing patient priorities care is that “it’s going to bring more joy in practice because you’re really addressing what matters to that individual while also providing good care.”
To get the most out of patient priorities care, Dr. Boyd recommended that clinicians focus on ‘the 4 M’s’: what matters most, mentation, mobility, and medications.
In an effort to address the last of these on a broad scale, Dr. Boyd is co-leading the US Deprescribing Research Network(USDeN), which aims to “improve medication use among older adults and the outcomes that are important to them,” according to the USDeN website.
To encourage deprescribing on a day-to-day level, Dr. Boyd called for strong communication between co–managing providers.
In an ideal world, there would be a better way to communicate than largely via electronic health records, she said.
“We need more than the EHR to connect us. That’s why it’s really important for primary care providers and specialists to be able to have time to actually talk to each other. This gets into how we reimburse and organize the communication and cognitive aspects of care,” Dr. Boyd noted.
Dr. Tinetti disclosed support from the John A. Hartford Foundation, the Donaghue Foundation, the National Institute on Aging, and the Institute for Healthcare Improvement. Dr. Boyd disclosed a relationship with UpToDate, for which she coauthored a chapter on multimorbidity.
said Mary Tinetti, MD, Gladys Phillips Crofoot Professor of Medicine and Public Health and chief of geriatrics at Yale University, New Haven, Conn.
During a virtual presentation at the American College of Physicians annual Internal Medicine meeting, the gerontologist noted that primary care providers face a number of challenges when managing elderly patients with multimorbidity. These challenges include a lack of representative data in clinical trials, conflicting guideline recommendations, patient nonadherence, and decreased benefit from therapies due to competing conditions, she said.
“Trying to follow multiple guidelines can result in unintentional harms to these people with multiple conditions,” Dr. Tinetti said. She gave examples of the wide-ranging goals patients can have.
“Some [patients] will maximize the focus on function, regardless of how long they are likely to live,” Dr. Tinetti said. “Others will say symptom burden management is most important to them. And others will say they want to live as long as possible, and survival is most important, even if that means a reduction in their function. These individuals also vary in the care they are willing and able to receive to achieve the outcomes that matter most to them.”
For these reasons, Dr. Tinetti recommended patient priorities care, which she and her colleagues have been developing and implementing over the past 5-6 years.
“If the benefits and harms of addressing each condition in isolation is of uncertain benefit and potentially burdensome to both clinician and patient, and we know that patients vary in their health priorities ... then what else would you want to focus on in your 20-minute visit ... except each patient’s priorities?” Dr. Tinetti asked. “This is one solution to the challenge.”
What is patient priorities care?
Patient priorities care is a multidisciplinary, cyclical approach to clinical decision-making composed of three steps, Dr. Tinetti explained. First, a clinician identifies the patient’s health priorities. Second, this information is transmitted to comanaging providers, who decide which of their respective treatments are consistent with the patient’s priorities. And third, those decisions are disseminated to everyone involved in the patient’s care, both within and outside of the health care system, allowing all care providers to align with the patient’s priorities, she noted.
“Each person does that from their own expertise,” Dr. Tinetti said. “The social worker will do something different than the cardiologist, the physical therapist, the endocrinologist – but everybody is aiming at the same outcome – the patient’s priorities.”
In 2019, Dr. Tinetti led a nonrandomized clinical trial to test the feasibility of patient priorities care. The study involved 366 older adults with multimorbidity, among whom 203 received usual care, while 163 received this type of care. Patients in the latter group were twice as likely to have medications stopped, and significantly less likely to have self-management tasks added and diagnostic tests ordered.
How electronic health records can help
In an interview, Dr. Tinetti suggested that comanaging physicians communicate through electronic health records (EHRs), first to ensure that all care providers understand a patient’s goals, then to determine if recommended therapies align with those goals.
“It would be a little bit of a culture change to do that,” Dr. Tinetti said, “but the technology is there and it isn’t too terribly time consuming.”
She went on to suggest that primary care providers are typically best suited to coordinate this process; however, if a patient receives the majority of their care from a particular specialist, then that clinician may be the most suitable coordinator.
Systemic obstacles and solutions
According to Cynthia Boyd, MD, interim director of the division of geriatric medicine and gerontology, Johns Hopkins University, Baltimore, clinicians may encounter obstacles when implementing patient priorities care.
“Our health care system doesn’t always make it easy to do this,” Dr. Boyd said. “It’s important to acknowledge this because it can be hard to do. There’s no question,” Dr. Boyd said in an interview.
Among the headwinds that clinicians may face are clinical practice guidelines, the structure of electronic health records, and quality metrics focused on specific conditions, she explained.
“There’s a lot of things that push us – in primary care and other parts of medicine – away from the approach that’s best for people with multiple chronic conditions,” Dr. Boyd said.
Dr. Tinetti said a challenge to providing this care that she expects is for clinicians, regardless of specialty, “to feel uneasy” about transitioning away from a conventional approach.
Among Dr. Tinetti’s arguments in favor of providing patient priorities care is that “it’s going to bring more joy in practice because you’re really addressing what matters to that individual while also providing good care.”
To get the most out of patient priorities care, Dr. Boyd recommended that clinicians focus on ‘the 4 M’s’: what matters most, mentation, mobility, and medications.
In an effort to address the last of these on a broad scale, Dr. Boyd is co-leading the US Deprescribing Research Network(USDeN), which aims to “improve medication use among older adults and the outcomes that are important to them,” according to the USDeN website.
To encourage deprescribing on a day-to-day level, Dr. Boyd called for strong communication between co–managing providers.
In an ideal world, there would be a better way to communicate than largely via electronic health records, she said.
“We need more than the EHR to connect us. That’s why it’s really important for primary care providers and specialists to be able to have time to actually talk to each other. This gets into how we reimburse and organize the communication and cognitive aspects of care,” Dr. Boyd noted.
Dr. Tinetti disclosed support from the John A. Hartford Foundation, the Donaghue Foundation, the National Institute on Aging, and the Institute for Healthcare Improvement. Dr. Boyd disclosed a relationship with UpToDate, for which she coauthored a chapter on multimorbidity.
said Mary Tinetti, MD, Gladys Phillips Crofoot Professor of Medicine and Public Health and chief of geriatrics at Yale University, New Haven, Conn.
During a virtual presentation at the American College of Physicians annual Internal Medicine meeting, the gerontologist noted that primary care providers face a number of challenges when managing elderly patients with multimorbidity. These challenges include a lack of representative data in clinical trials, conflicting guideline recommendations, patient nonadherence, and decreased benefit from therapies due to competing conditions, she said.
“Trying to follow multiple guidelines can result in unintentional harms to these people with multiple conditions,” Dr. Tinetti said. She gave examples of the wide-ranging goals patients can have.
“Some [patients] will maximize the focus on function, regardless of how long they are likely to live,” Dr. Tinetti said. “Others will say symptom burden management is most important to them. And others will say they want to live as long as possible, and survival is most important, even if that means a reduction in their function. These individuals also vary in the care they are willing and able to receive to achieve the outcomes that matter most to them.”
For these reasons, Dr. Tinetti recommended patient priorities care, which she and her colleagues have been developing and implementing over the past 5-6 years.
“If the benefits and harms of addressing each condition in isolation is of uncertain benefit and potentially burdensome to both clinician and patient, and we know that patients vary in their health priorities ... then what else would you want to focus on in your 20-minute visit ... except each patient’s priorities?” Dr. Tinetti asked. “This is one solution to the challenge.”
What is patient priorities care?
Patient priorities care is a multidisciplinary, cyclical approach to clinical decision-making composed of three steps, Dr. Tinetti explained. First, a clinician identifies the patient’s health priorities. Second, this information is transmitted to comanaging providers, who decide which of their respective treatments are consistent with the patient’s priorities. And third, those decisions are disseminated to everyone involved in the patient’s care, both within and outside of the health care system, allowing all care providers to align with the patient’s priorities, she noted.
“Each person does that from their own expertise,” Dr. Tinetti said. “The social worker will do something different than the cardiologist, the physical therapist, the endocrinologist – but everybody is aiming at the same outcome – the patient’s priorities.”
In 2019, Dr. Tinetti led a nonrandomized clinical trial to test the feasibility of patient priorities care. The study involved 366 older adults with multimorbidity, among whom 203 received usual care, while 163 received this type of care. Patients in the latter group were twice as likely to have medications stopped, and significantly less likely to have self-management tasks added and diagnostic tests ordered.
How electronic health records can help
In an interview, Dr. Tinetti suggested that comanaging physicians communicate through electronic health records (EHRs), first to ensure that all care providers understand a patient’s goals, then to determine if recommended therapies align with those goals.
“It would be a little bit of a culture change to do that,” Dr. Tinetti said, “but the technology is there and it isn’t too terribly time consuming.”
She went on to suggest that primary care providers are typically best suited to coordinate this process; however, if a patient receives the majority of their care from a particular specialist, then that clinician may be the most suitable coordinator.
Systemic obstacles and solutions
According to Cynthia Boyd, MD, interim director of the division of geriatric medicine and gerontology, Johns Hopkins University, Baltimore, clinicians may encounter obstacles when implementing patient priorities care.
“Our health care system doesn’t always make it easy to do this,” Dr. Boyd said. “It’s important to acknowledge this because it can be hard to do. There’s no question,” Dr. Boyd said in an interview.
Among the headwinds that clinicians may face are clinical practice guidelines, the structure of electronic health records, and quality metrics focused on specific conditions, she explained.
“There’s a lot of things that push us – in primary care and other parts of medicine – away from the approach that’s best for people with multiple chronic conditions,” Dr. Boyd said.
Dr. Tinetti said a challenge to providing this care that she expects is for clinicians, regardless of specialty, “to feel uneasy” about transitioning away from a conventional approach.
Among Dr. Tinetti’s arguments in favor of providing patient priorities care is that “it’s going to bring more joy in practice because you’re really addressing what matters to that individual while also providing good care.”
To get the most out of patient priorities care, Dr. Boyd recommended that clinicians focus on ‘the 4 M’s’: what matters most, mentation, mobility, and medications.
In an effort to address the last of these on a broad scale, Dr. Boyd is co-leading the US Deprescribing Research Network(USDeN), which aims to “improve medication use among older adults and the outcomes that are important to them,” according to the USDeN website.
To encourage deprescribing on a day-to-day level, Dr. Boyd called for strong communication between co–managing providers.
In an ideal world, there would be a better way to communicate than largely via electronic health records, she said.
“We need more than the EHR to connect us. That’s why it’s really important for primary care providers and specialists to be able to have time to actually talk to each other. This gets into how we reimburse and organize the communication and cognitive aspects of care,” Dr. Boyd noted.
Dr. Tinetti disclosed support from the John A. Hartford Foundation, the Donaghue Foundation, the National Institute on Aging, and the Institute for Healthcare Improvement. Dr. Boyd disclosed a relationship with UpToDate, for which she coauthored a chapter on multimorbidity.
FROM INTERNAL MEDICINE 2021
Restrict J&J COVID vaccine in women under 50?
Use of mRNA COVID-19 vaccines should be considered as the preferable option in the United States rather than Johnson & Johnson’s (J&J) Janssen COVID-19 vaccine in women aged under 50 years, according to one group of experts.
The group made their recommendation in an editorial in JAMA published online April 30, 2021, accompanying a paper describing details of 12 case reports of cerebral venous sinus thrombosis (CVST) with thrombocytopenia following the J&J COVID-19 vaccine, also known as the Ad26.COV2.S vaccine.
The editorialists are Ruth A. Karron, MD, professor of international health at Johns Hopkins University, Baltimore; Nigel S. Key, MD, professor of hematology at the University of North Carolina at Chapel Hill; and Joshua M. Sharfstein, MD, associate dean for public health practice at Johns Hopkins
They noted that, after an initial pause following reports of thrombosis with thrombocytopenia syndrome (TTS) linked to the J&J vaccine, and on the recommendation of the Advisory Committee on Immunization Practices, the United States has permitted the use of the J&J vaccine in all adults with information on the risk of TTS added to educational materials.
The editorialists pointed out that no cases of TTS have been confirmed following administration of more than 180 million doses of the mRNA vaccines in the United States.
They said that, while the J&J vaccine will still be needed for individuals with allergies to components of the mRNA vaccines and for those who live in remote locations where the cold chain for transport and storage of mRNA vaccines cannot be maintained, “U.S. public health agencies and clinicians should consider recommending mRNA vaccines as safer options for those who may be at substantially higher risk for TTS after Ad26.COV2.S vaccination, currently women younger than 50 years.”
In the main JAMA paper, a group led by Isaac See, MD, Centers for Disease Control and Prevention COVID-19 Response Team, reported full details of 12 cases of CVST with thrombocytopenia following the J&J COVID-19 vaccine reported to the U.S. Vaccine Adverse Event Reporting System (VAERS).
The 12 U.S. case reports, 3 of which were fatal, show many similarities to cases described in Europe after the AstraZeneca vaccine.
The authors noted that, by April 12, approximately 7 million doses of the J&J vaccine had been given in the United States. The 12 cases of CVST and thrombocytopenia following receipt of the vaccine were reported to VAERS between March 2 and April 21. All 12 cases were in White women, 11 of whom were aged under 50 years.
As of April 25, a further two cases have been confirmed and reported to VAERS; one in a man younger than 40 years, the other in a woman aged between 40 and 59 years.
In the 12 cases reported in detail, symptoms started between 6 and 15 days post vaccination.
At least one risk factor for CVST was identified in seven patients (obesity in six, hypothyroidism in one, and use of combined oral contraceptives in one). None of the patients was pregnant or within 12 weeks post partum, had prior thrombosis, a personal or family history of thrombophilia, or documented prior exposure to heparin.
In addition to CVST, seven patients had intracerebral hemorrhage and eight had non-CVST thromboses.
One patient reported a history of SARS-CoV-2 infection approximately 4 months prior to vaccination. Of the other 11 patients, 4 had negative serologic tests and 7 were not tested.
All 12 patients were hospitalized and 10 were admitted to an ICU. At the time of the last follow-up, three patients had died (all of whom had intraparenchymal hemorrhage), three remained in the ICU, two were still hospitalized but not in an ICU, and four had been discharged home.
The authors pointed out that the U.S. cases of CVST with thrombocytopenia following the J&J vaccine have many similarities to those reported in Europe after the AstraZeneca vaccine, occurring primarily in women younger than 40 years and in patients without diagnosed thrombophilia. Both European and U.S. patients had a median platelet nadir count of 19 x 103/mcL and several also had non-CVST large-vessel thrombosis.
In the European cases of CVST with thrombocytopenia, 50% of patients died, compared with 25% of U.S. patients.
Like the European cases, the U.S. cases had positive heparin-PF4 HIT antibody enzyme-linked immunosorbent assay tests in the absence of prior exposure to heparin, as would be seen in autoimmune HIT.
However, in the initial European CVST reports, 88% of patients tested with functional platelet HIT antibody tests had positive results, compared with only 11% of the U.S. cases. But the authors noted that lack of standardization in functional platelet HIT antibody assays may lead to differences in results by different laboratories.
“It may be important to notify testing laboratories that postvaccination TTS is being evaluated, so that testing methods can be adjusted if needed,” they said.
They concluded that these case reports suggest that the pathogenesis of TTS may be similar to autoimmune HIT, triggered by the formation of antibodies directed against PF4, a constituent of platelet alpha granules released during platelet activation. In contrast to classic HIT in which exogenous heparin triggers antibody formation, in autoimmune HIT, an endogenous polyanion triggers PF4 antibody formation.
They noted that the precise mechanism of TTS in relation to COVID-19 vaccination has not yet been established. The Global Advisory Committee on Vaccine Safety has stated that a platform-specific mechanism related to adenovirus vector vaccines cannot be excluded. Both the J&J and AstraZeneca vaccines use an adenoviral vector, but they are different; J&J uses a human vector, while AstraZeneca uses a chimpanzee vector.
They also pointed out that CVST and thrombocytopenia following SARS-CoV-2 infection has been reported in at least two cases, but HIT testing was not done in these cases. There have not so far been any reports to VAERS of CVST with thrombocytopenia following mRNA COVID-19 vaccines.
The authors said these findings have important clinical and public health implications, noting that the CDC has updated its interim clinical considerations for use of authorized COVID-19 vaccines to indicate that women aged 18-49 years should be aware of the increased risk of TTS after receipt of the J&J vaccine, and to use a nonheparin anticoagulant in suspected cases.
They noted that a subacute presentation of headache is present in 90% of patients with typical CVST. While headache is a common symptom after the J&J vaccination, most headaches begin and resolve within 2 days. Whereas in the U.S. cases of CVST after vaccination, headache symptoms began at least 6 days after vaccination and persisted for at least a week for most.
“Urgent consultation with a neurologist is prudent when a patient is suspected or confirmed to have CVST. In addition, since the median time from symptom onset to hospitalization was 7 days in the U.S. CVST case series, patient and clinician education might shorten the time to clinical evaluation and therefore treatment,” they stated.
The authors also note that VAERS is a passive surveillance system, so cases of CVST with thrombocytopenia may be underreported.
In their accompanying editorial, Dr. Karron and colleagues pointed out that, in addition to the 12 patients with CVST with thrombocytopenia described in this case series, at least three patients without CVST but meeting diagnostic criteria for TTS have been reported to VAERS (as of April 21), all in women aged 18-59 years (median age, 37 years).
The editorialists reported that the rate of CVST with thrombocytopenia after the J&J vaccine is approximately 5 per million women aged 18-50 years. This is compared with a background rate of approximately 0.05-0.13 per million per month.
They said that the availability of an interim standardized case definition of this adverse effect will facilitate prospective case ascertainment through review of large linked databases and active case finding.
This will also permit greater understanding of whether individuals who are otherwise at increased risk for hypercoagulation in general and for CVST in particular (for example, women taking hormonal contraceptive medications or who are pregnant) are also at increased risk for TTS.
Obtaining this information will support dynamic country-specific assessments of the risks of each vaccine, compared with the risk of COVID-19 disease for their populations and subpopulations, they added.
A version of this article first appeared on Medscape.com.
Use of mRNA COVID-19 vaccines should be considered as the preferable option in the United States rather than Johnson & Johnson’s (J&J) Janssen COVID-19 vaccine in women aged under 50 years, according to one group of experts.
The group made their recommendation in an editorial in JAMA published online April 30, 2021, accompanying a paper describing details of 12 case reports of cerebral venous sinus thrombosis (CVST) with thrombocytopenia following the J&J COVID-19 vaccine, also known as the Ad26.COV2.S vaccine.
The editorialists are Ruth A. Karron, MD, professor of international health at Johns Hopkins University, Baltimore; Nigel S. Key, MD, professor of hematology at the University of North Carolina at Chapel Hill; and Joshua M. Sharfstein, MD, associate dean for public health practice at Johns Hopkins
They noted that, after an initial pause following reports of thrombosis with thrombocytopenia syndrome (TTS) linked to the J&J vaccine, and on the recommendation of the Advisory Committee on Immunization Practices, the United States has permitted the use of the J&J vaccine in all adults with information on the risk of TTS added to educational materials.
The editorialists pointed out that no cases of TTS have been confirmed following administration of more than 180 million doses of the mRNA vaccines in the United States.
They said that, while the J&J vaccine will still be needed for individuals with allergies to components of the mRNA vaccines and for those who live in remote locations where the cold chain for transport and storage of mRNA vaccines cannot be maintained, “U.S. public health agencies and clinicians should consider recommending mRNA vaccines as safer options for those who may be at substantially higher risk for TTS after Ad26.COV2.S vaccination, currently women younger than 50 years.”
In the main JAMA paper, a group led by Isaac See, MD, Centers for Disease Control and Prevention COVID-19 Response Team, reported full details of 12 cases of CVST with thrombocytopenia following the J&J COVID-19 vaccine reported to the U.S. Vaccine Adverse Event Reporting System (VAERS).
The 12 U.S. case reports, 3 of which were fatal, show many similarities to cases described in Europe after the AstraZeneca vaccine.
The authors noted that, by April 12, approximately 7 million doses of the J&J vaccine had been given in the United States. The 12 cases of CVST and thrombocytopenia following receipt of the vaccine were reported to VAERS between March 2 and April 21. All 12 cases were in White women, 11 of whom were aged under 50 years.
As of April 25, a further two cases have been confirmed and reported to VAERS; one in a man younger than 40 years, the other in a woman aged between 40 and 59 years.
In the 12 cases reported in detail, symptoms started between 6 and 15 days post vaccination.
At least one risk factor for CVST was identified in seven patients (obesity in six, hypothyroidism in one, and use of combined oral contraceptives in one). None of the patients was pregnant or within 12 weeks post partum, had prior thrombosis, a personal or family history of thrombophilia, or documented prior exposure to heparin.
In addition to CVST, seven patients had intracerebral hemorrhage and eight had non-CVST thromboses.
One patient reported a history of SARS-CoV-2 infection approximately 4 months prior to vaccination. Of the other 11 patients, 4 had negative serologic tests and 7 were not tested.
All 12 patients were hospitalized and 10 were admitted to an ICU. At the time of the last follow-up, three patients had died (all of whom had intraparenchymal hemorrhage), three remained in the ICU, two were still hospitalized but not in an ICU, and four had been discharged home.
The authors pointed out that the U.S. cases of CVST with thrombocytopenia following the J&J vaccine have many similarities to those reported in Europe after the AstraZeneca vaccine, occurring primarily in women younger than 40 years and in patients without diagnosed thrombophilia. Both European and U.S. patients had a median platelet nadir count of 19 x 103/mcL and several also had non-CVST large-vessel thrombosis.
In the European cases of CVST with thrombocytopenia, 50% of patients died, compared with 25% of U.S. patients.
Like the European cases, the U.S. cases had positive heparin-PF4 HIT antibody enzyme-linked immunosorbent assay tests in the absence of prior exposure to heparin, as would be seen in autoimmune HIT.
However, in the initial European CVST reports, 88% of patients tested with functional platelet HIT antibody tests had positive results, compared with only 11% of the U.S. cases. But the authors noted that lack of standardization in functional platelet HIT antibody assays may lead to differences in results by different laboratories.
“It may be important to notify testing laboratories that postvaccination TTS is being evaluated, so that testing methods can be adjusted if needed,” they said.
They concluded that these case reports suggest that the pathogenesis of TTS may be similar to autoimmune HIT, triggered by the formation of antibodies directed against PF4, a constituent of platelet alpha granules released during platelet activation. In contrast to classic HIT in which exogenous heparin triggers antibody formation, in autoimmune HIT, an endogenous polyanion triggers PF4 antibody formation.
They noted that the precise mechanism of TTS in relation to COVID-19 vaccination has not yet been established. The Global Advisory Committee on Vaccine Safety has stated that a platform-specific mechanism related to adenovirus vector vaccines cannot be excluded. Both the J&J and AstraZeneca vaccines use an adenoviral vector, but they are different; J&J uses a human vector, while AstraZeneca uses a chimpanzee vector.
They also pointed out that CVST and thrombocytopenia following SARS-CoV-2 infection has been reported in at least two cases, but HIT testing was not done in these cases. There have not so far been any reports to VAERS of CVST with thrombocytopenia following mRNA COVID-19 vaccines.
The authors said these findings have important clinical and public health implications, noting that the CDC has updated its interim clinical considerations for use of authorized COVID-19 vaccines to indicate that women aged 18-49 years should be aware of the increased risk of TTS after receipt of the J&J vaccine, and to use a nonheparin anticoagulant in suspected cases.
They noted that a subacute presentation of headache is present in 90% of patients with typical CVST. While headache is a common symptom after the J&J vaccination, most headaches begin and resolve within 2 days. Whereas in the U.S. cases of CVST after vaccination, headache symptoms began at least 6 days after vaccination and persisted for at least a week for most.
“Urgent consultation with a neurologist is prudent when a patient is suspected or confirmed to have CVST. In addition, since the median time from symptom onset to hospitalization was 7 days in the U.S. CVST case series, patient and clinician education might shorten the time to clinical evaluation and therefore treatment,” they stated.
The authors also note that VAERS is a passive surveillance system, so cases of CVST with thrombocytopenia may be underreported.
In their accompanying editorial, Dr. Karron and colleagues pointed out that, in addition to the 12 patients with CVST with thrombocytopenia described in this case series, at least three patients without CVST but meeting diagnostic criteria for TTS have been reported to VAERS (as of April 21), all in women aged 18-59 years (median age, 37 years).
The editorialists reported that the rate of CVST with thrombocytopenia after the J&J vaccine is approximately 5 per million women aged 18-50 years. This is compared with a background rate of approximately 0.05-0.13 per million per month.
They said that the availability of an interim standardized case definition of this adverse effect will facilitate prospective case ascertainment through review of large linked databases and active case finding.
This will also permit greater understanding of whether individuals who are otherwise at increased risk for hypercoagulation in general and for CVST in particular (for example, women taking hormonal contraceptive medications or who are pregnant) are also at increased risk for TTS.
Obtaining this information will support dynamic country-specific assessments of the risks of each vaccine, compared with the risk of COVID-19 disease for their populations and subpopulations, they added.
A version of this article first appeared on Medscape.com.
Use of mRNA COVID-19 vaccines should be considered as the preferable option in the United States rather than Johnson & Johnson’s (J&J) Janssen COVID-19 vaccine in women aged under 50 years, according to one group of experts.
The group made their recommendation in an editorial in JAMA published online April 30, 2021, accompanying a paper describing details of 12 case reports of cerebral venous sinus thrombosis (CVST) with thrombocytopenia following the J&J COVID-19 vaccine, also known as the Ad26.COV2.S vaccine.
The editorialists are Ruth A. Karron, MD, professor of international health at Johns Hopkins University, Baltimore; Nigel S. Key, MD, professor of hematology at the University of North Carolina at Chapel Hill; and Joshua M. Sharfstein, MD, associate dean for public health practice at Johns Hopkins
They noted that, after an initial pause following reports of thrombosis with thrombocytopenia syndrome (TTS) linked to the J&J vaccine, and on the recommendation of the Advisory Committee on Immunization Practices, the United States has permitted the use of the J&J vaccine in all adults with information on the risk of TTS added to educational materials.
The editorialists pointed out that no cases of TTS have been confirmed following administration of more than 180 million doses of the mRNA vaccines in the United States.
They said that, while the J&J vaccine will still be needed for individuals with allergies to components of the mRNA vaccines and for those who live in remote locations where the cold chain for transport and storage of mRNA vaccines cannot be maintained, “U.S. public health agencies and clinicians should consider recommending mRNA vaccines as safer options for those who may be at substantially higher risk for TTS after Ad26.COV2.S vaccination, currently women younger than 50 years.”
In the main JAMA paper, a group led by Isaac See, MD, Centers for Disease Control and Prevention COVID-19 Response Team, reported full details of 12 cases of CVST with thrombocytopenia following the J&J COVID-19 vaccine reported to the U.S. Vaccine Adverse Event Reporting System (VAERS).
The 12 U.S. case reports, 3 of which were fatal, show many similarities to cases described in Europe after the AstraZeneca vaccine.
The authors noted that, by April 12, approximately 7 million doses of the J&J vaccine had been given in the United States. The 12 cases of CVST and thrombocytopenia following receipt of the vaccine were reported to VAERS between March 2 and April 21. All 12 cases were in White women, 11 of whom were aged under 50 years.
As of April 25, a further two cases have been confirmed and reported to VAERS; one in a man younger than 40 years, the other in a woman aged between 40 and 59 years.
In the 12 cases reported in detail, symptoms started between 6 and 15 days post vaccination.
At least one risk factor for CVST was identified in seven patients (obesity in six, hypothyroidism in one, and use of combined oral contraceptives in one). None of the patients was pregnant or within 12 weeks post partum, had prior thrombosis, a personal or family history of thrombophilia, or documented prior exposure to heparin.
In addition to CVST, seven patients had intracerebral hemorrhage and eight had non-CVST thromboses.
One patient reported a history of SARS-CoV-2 infection approximately 4 months prior to vaccination. Of the other 11 patients, 4 had negative serologic tests and 7 were not tested.
All 12 patients were hospitalized and 10 were admitted to an ICU. At the time of the last follow-up, three patients had died (all of whom had intraparenchymal hemorrhage), three remained in the ICU, two were still hospitalized but not in an ICU, and four had been discharged home.
The authors pointed out that the U.S. cases of CVST with thrombocytopenia following the J&J vaccine have many similarities to those reported in Europe after the AstraZeneca vaccine, occurring primarily in women younger than 40 years and in patients without diagnosed thrombophilia. Both European and U.S. patients had a median platelet nadir count of 19 x 103/mcL and several also had non-CVST large-vessel thrombosis.
In the European cases of CVST with thrombocytopenia, 50% of patients died, compared with 25% of U.S. patients.
Like the European cases, the U.S. cases had positive heparin-PF4 HIT antibody enzyme-linked immunosorbent assay tests in the absence of prior exposure to heparin, as would be seen in autoimmune HIT.
However, in the initial European CVST reports, 88% of patients tested with functional platelet HIT antibody tests had positive results, compared with only 11% of the U.S. cases. But the authors noted that lack of standardization in functional platelet HIT antibody assays may lead to differences in results by different laboratories.
“It may be important to notify testing laboratories that postvaccination TTS is being evaluated, so that testing methods can be adjusted if needed,” they said.
They concluded that these case reports suggest that the pathogenesis of TTS may be similar to autoimmune HIT, triggered by the formation of antibodies directed against PF4, a constituent of platelet alpha granules released during platelet activation. In contrast to classic HIT in which exogenous heparin triggers antibody formation, in autoimmune HIT, an endogenous polyanion triggers PF4 antibody formation.
They noted that the precise mechanism of TTS in relation to COVID-19 vaccination has not yet been established. The Global Advisory Committee on Vaccine Safety has stated that a platform-specific mechanism related to adenovirus vector vaccines cannot be excluded. Both the J&J and AstraZeneca vaccines use an adenoviral vector, but they are different; J&J uses a human vector, while AstraZeneca uses a chimpanzee vector.
They also pointed out that CVST and thrombocytopenia following SARS-CoV-2 infection has been reported in at least two cases, but HIT testing was not done in these cases. There have not so far been any reports to VAERS of CVST with thrombocytopenia following mRNA COVID-19 vaccines.
The authors said these findings have important clinical and public health implications, noting that the CDC has updated its interim clinical considerations for use of authorized COVID-19 vaccines to indicate that women aged 18-49 years should be aware of the increased risk of TTS after receipt of the J&J vaccine, and to use a nonheparin anticoagulant in suspected cases.
They noted that a subacute presentation of headache is present in 90% of patients with typical CVST. While headache is a common symptom after the J&J vaccination, most headaches begin and resolve within 2 days. Whereas in the U.S. cases of CVST after vaccination, headache symptoms began at least 6 days after vaccination and persisted for at least a week for most.
“Urgent consultation with a neurologist is prudent when a patient is suspected or confirmed to have CVST. In addition, since the median time from symptom onset to hospitalization was 7 days in the U.S. CVST case series, patient and clinician education might shorten the time to clinical evaluation and therefore treatment,” they stated.
The authors also note that VAERS is a passive surveillance system, so cases of CVST with thrombocytopenia may be underreported.
In their accompanying editorial, Dr. Karron and colleagues pointed out that, in addition to the 12 patients with CVST with thrombocytopenia described in this case series, at least three patients without CVST but meeting diagnostic criteria for TTS have been reported to VAERS (as of April 21), all in women aged 18-59 years (median age, 37 years).
The editorialists reported that the rate of CVST with thrombocytopenia after the J&J vaccine is approximately 5 per million women aged 18-50 years. This is compared with a background rate of approximately 0.05-0.13 per million per month.
They said that the availability of an interim standardized case definition of this adverse effect will facilitate prospective case ascertainment through review of large linked databases and active case finding.
This will also permit greater understanding of whether individuals who are otherwise at increased risk for hypercoagulation in general and for CVST in particular (for example, women taking hormonal contraceptive medications or who are pregnant) are also at increased risk for TTS.
Obtaining this information will support dynamic country-specific assessments of the risks of each vaccine, compared with the risk of COVID-19 disease for their populations and subpopulations, they added.
A version of this article first appeared on Medscape.com.
Pediatric cancer survivors at risk for opioid misuse
Survivors of childhood cancers are at increased risk for prescription opioid misuse compared with their peers, a review of a claims database revealed.
Among more than 8,000 patients age 21 or younger who had completed treatment for hematologic, central nervous system, bone, or gonadal cancers, survivors were significantly more likely than were their peers to have an opioid prescription, longer duration of prescription, and higher daily doses of opioids, and to have opioid prescriptions overlapping for a week or more, reported Xu Ji, PhD, of Emory University in Atlanta.
Teenage and young adult patients were at higher risk than were patients younger than 12, and the risk was highest among patients who had been treated for bone malignancies, as well as those who had undergone any hematopoietic stem cell transplant.
“These findings suggest that health care providers who regularly see survivors should explore nonopioid options to help prevent opioid misuse, and screen for potential misuse in those who actually receive opioids,” she said in an oral abstract presented during the annual meeting of the American Society of Pediatric Hematology/Oncology.
“This is a really important topic, and something that’s probably been underinvestigated and underexplored in our patient population,” said session comoderator Sheri Spunt, MD, Endowed Professor of Pediatric Cancer at Stanford (Calif.) University.
Database review
Dr. Ji and colleagues used the IBM MarketScan Commercial Claims and Encounters database from 2009 to 2018 to examine prescription opioid use, potential misuse, and substance use disorders in pediatric cancer survivors in the first year after completion of therapy, and to identify factors associated with risk for misuse or substance use disorders. Specifically, the period of interest was the first year after completion of all treatments, including surgery, chemotherapy, radiation, and stem cell transplant (Abstract 2015).
They looked at deidentified records on any opioid prescription and for treatment of any opioid use or substance use disorder (alcohol, psychotherapeutic drugs, marijuana, or illicit drug use disorders).
They defined indicators of potential misuse as either prescriptions for long-acting or extended-release opioids for acute pain conditions; opioid and benzodiazepine prescriptions overlapping by a week or more; opioid prescriptions overlapping by a week or more; high daily opioid dosage (prescribed daily dose of 100 or greater morphine milligram equivalent [MME]; and/or opioid dose escalation (an increase of at least 50% in mean MMEs per month twice consecutively within 1 year).
They compared outcomes between a total of 8,635 survivors and 44,175 controls, matched on a 1:5 basis with survivors by age, sex, and region, and continuous enrollment during the 1-year posttherapy period.
In each of three age categories – 0 to 11 years, 12 to 17 years, and 18 years and older – survivors were significantly more likely to have received an opioid prescription, at 15% for the youngest survivors vs. 2% of controls, 25% vs. 8% for 12- to 17-year-olds, and 28% vs. 12% for those 18 and older (P < .01 for all three comparisons).
Survivors were also significantly more likely to have any indicator of potential misuse (1.6% vs. 0.1%, 4.6% vs. 0.5%, and 7.4% vs. 1.2%, respectively, P < .001 for all) and both the youngest and oldest groups (but not 12- to 17-year-olds) were significantly more like to have opioid or substance use disorder (0.4% vs. 0% for 0-11 years, 5.76% vs. 4.2% for 18 years and older, P < .001 for both).
Among patients with any opioid prescription, survivors were significantly more likely than were controls of any age to have indicators for potential misuse. For example, 13% of survivors aged 18 years and older had prescriptions for high opioid doses, compared with 5% of controls, and 12% had prescription overlap, vs. 2%.
Compared with patients with leukemia, patients treated for bone malignancies had a 6% greater risk for having any indicator of misuse, while patients with other malignancies were at slightly lower risk for misuse than those who completed leukemia therapy.
Patients who received any stem cell transplant had an 8.4% greater risk for misuse compared with patients who had surgery only.
Opioids pre- and posttreatment?
“Being someone who takes care of a lot of bone cancer patients, I do see patients with these issues,” Dr. Spunt said.
Audience member Jack H. Staddon, MD, PhD, of the Billings (Montana) Clinic, noted the possibility that opioid use during treatment may have been carried on into the posttreatment period, and asked whether use of narcotics during treatment was an independent risk factor for posttreatment narcotic use or misuse.
The researchers plan to investigate this question in future studies, Dr. Ji replied.
They did not report a study funding source. Dr. Ji and coauthors and Dr. Staddon reported no relevant disclosures.
Survivors of childhood cancers are at increased risk for prescription opioid misuse compared with their peers, a review of a claims database revealed.
Among more than 8,000 patients age 21 or younger who had completed treatment for hematologic, central nervous system, bone, or gonadal cancers, survivors were significantly more likely than were their peers to have an opioid prescription, longer duration of prescription, and higher daily doses of opioids, and to have opioid prescriptions overlapping for a week or more, reported Xu Ji, PhD, of Emory University in Atlanta.
Teenage and young adult patients were at higher risk than were patients younger than 12, and the risk was highest among patients who had been treated for bone malignancies, as well as those who had undergone any hematopoietic stem cell transplant.
“These findings suggest that health care providers who regularly see survivors should explore nonopioid options to help prevent opioid misuse, and screen for potential misuse in those who actually receive opioids,” she said in an oral abstract presented during the annual meeting of the American Society of Pediatric Hematology/Oncology.
“This is a really important topic, and something that’s probably been underinvestigated and underexplored in our patient population,” said session comoderator Sheri Spunt, MD, Endowed Professor of Pediatric Cancer at Stanford (Calif.) University.
Database review
Dr. Ji and colleagues used the IBM MarketScan Commercial Claims and Encounters database from 2009 to 2018 to examine prescription opioid use, potential misuse, and substance use disorders in pediatric cancer survivors in the first year after completion of therapy, and to identify factors associated with risk for misuse or substance use disorders. Specifically, the period of interest was the first year after completion of all treatments, including surgery, chemotherapy, radiation, and stem cell transplant (Abstract 2015).
They looked at deidentified records on any opioid prescription and for treatment of any opioid use or substance use disorder (alcohol, psychotherapeutic drugs, marijuana, or illicit drug use disorders).
They defined indicators of potential misuse as either prescriptions for long-acting or extended-release opioids for acute pain conditions; opioid and benzodiazepine prescriptions overlapping by a week or more; opioid prescriptions overlapping by a week or more; high daily opioid dosage (prescribed daily dose of 100 or greater morphine milligram equivalent [MME]; and/or opioid dose escalation (an increase of at least 50% in mean MMEs per month twice consecutively within 1 year).
They compared outcomes between a total of 8,635 survivors and 44,175 controls, matched on a 1:5 basis with survivors by age, sex, and region, and continuous enrollment during the 1-year posttherapy period.
In each of three age categories – 0 to 11 years, 12 to 17 years, and 18 years and older – survivors were significantly more likely to have received an opioid prescription, at 15% for the youngest survivors vs. 2% of controls, 25% vs. 8% for 12- to 17-year-olds, and 28% vs. 12% for those 18 and older (P < .01 for all three comparisons).
Survivors were also significantly more likely to have any indicator of potential misuse (1.6% vs. 0.1%, 4.6% vs. 0.5%, and 7.4% vs. 1.2%, respectively, P < .001 for all) and both the youngest and oldest groups (but not 12- to 17-year-olds) were significantly more like to have opioid or substance use disorder (0.4% vs. 0% for 0-11 years, 5.76% vs. 4.2% for 18 years and older, P < .001 for both).
Among patients with any opioid prescription, survivors were significantly more likely than were controls of any age to have indicators for potential misuse. For example, 13% of survivors aged 18 years and older had prescriptions for high opioid doses, compared with 5% of controls, and 12% had prescription overlap, vs. 2%.
Compared with patients with leukemia, patients treated for bone malignancies had a 6% greater risk for having any indicator of misuse, while patients with other malignancies were at slightly lower risk for misuse than those who completed leukemia therapy.
Patients who received any stem cell transplant had an 8.4% greater risk for misuse compared with patients who had surgery only.
Opioids pre- and posttreatment?
“Being someone who takes care of a lot of bone cancer patients, I do see patients with these issues,” Dr. Spunt said.
Audience member Jack H. Staddon, MD, PhD, of the Billings (Montana) Clinic, noted the possibility that opioid use during treatment may have been carried on into the posttreatment period, and asked whether use of narcotics during treatment was an independent risk factor for posttreatment narcotic use or misuse.
The researchers plan to investigate this question in future studies, Dr. Ji replied.
They did not report a study funding source. Dr. Ji and coauthors and Dr. Staddon reported no relevant disclosures.
Survivors of childhood cancers are at increased risk for prescription opioid misuse compared with their peers, a review of a claims database revealed.
Among more than 8,000 patients age 21 or younger who had completed treatment for hematologic, central nervous system, bone, or gonadal cancers, survivors were significantly more likely than were their peers to have an opioid prescription, longer duration of prescription, and higher daily doses of opioids, and to have opioid prescriptions overlapping for a week or more, reported Xu Ji, PhD, of Emory University in Atlanta.
Teenage and young adult patients were at higher risk than were patients younger than 12, and the risk was highest among patients who had been treated for bone malignancies, as well as those who had undergone any hematopoietic stem cell transplant.
“These findings suggest that health care providers who regularly see survivors should explore nonopioid options to help prevent opioid misuse, and screen for potential misuse in those who actually receive opioids,” she said in an oral abstract presented during the annual meeting of the American Society of Pediatric Hematology/Oncology.
“This is a really important topic, and something that’s probably been underinvestigated and underexplored in our patient population,” said session comoderator Sheri Spunt, MD, Endowed Professor of Pediatric Cancer at Stanford (Calif.) University.
Database review
Dr. Ji and colleagues used the IBM MarketScan Commercial Claims and Encounters database from 2009 to 2018 to examine prescription opioid use, potential misuse, and substance use disorders in pediatric cancer survivors in the first year after completion of therapy, and to identify factors associated with risk for misuse or substance use disorders. Specifically, the period of interest was the first year after completion of all treatments, including surgery, chemotherapy, radiation, and stem cell transplant (Abstract 2015).
They looked at deidentified records on any opioid prescription and for treatment of any opioid use or substance use disorder (alcohol, psychotherapeutic drugs, marijuana, or illicit drug use disorders).
They defined indicators of potential misuse as either prescriptions for long-acting or extended-release opioids for acute pain conditions; opioid and benzodiazepine prescriptions overlapping by a week or more; opioid prescriptions overlapping by a week or more; high daily opioid dosage (prescribed daily dose of 100 or greater morphine milligram equivalent [MME]; and/or opioid dose escalation (an increase of at least 50% in mean MMEs per month twice consecutively within 1 year).
They compared outcomes between a total of 8,635 survivors and 44,175 controls, matched on a 1:5 basis with survivors by age, sex, and region, and continuous enrollment during the 1-year posttherapy period.
In each of three age categories – 0 to 11 years, 12 to 17 years, and 18 years and older – survivors were significantly more likely to have received an opioid prescription, at 15% for the youngest survivors vs. 2% of controls, 25% vs. 8% for 12- to 17-year-olds, and 28% vs. 12% for those 18 and older (P < .01 for all three comparisons).
Survivors were also significantly more likely to have any indicator of potential misuse (1.6% vs. 0.1%, 4.6% vs. 0.5%, and 7.4% vs. 1.2%, respectively, P < .001 for all) and both the youngest and oldest groups (but not 12- to 17-year-olds) were significantly more like to have opioid or substance use disorder (0.4% vs. 0% for 0-11 years, 5.76% vs. 4.2% for 18 years and older, P < .001 for both).
Among patients with any opioid prescription, survivors were significantly more likely than were controls of any age to have indicators for potential misuse. For example, 13% of survivors aged 18 years and older had prescriptions for high opioid doses, compared with 5% of controls, and 12% had prescription overlap, vs. 2%.
Compared with patients with leukemia, patients treated for bone malignancies had a 6% greater risk for having any indicator of misuse, while patients with other malignancies were at slightly lower risk for misuse than those who completed leukemia therapy.
Patients who received any stem cell transplant had an 8.4% greater risk for misuse compared with patients who had surgery only.
Opioids pre- and posttreatment?
“Being someone who takes care of a lot of bone cancer patients, I do see patients with these issues,” Dr. Spunt said.
Audience member Jack H. Staddon, MD, PhD, of the Billings (Montana) Clinic, noted the possibility that opioid use during treatment may have been carried on into the posttreatment period, and asked whether use of narcotics during treatment was an independent risk factor for posttreatment narcotic use or misuse.
The researchers plan to investigate this question in future studies, Dr. Ji replied.
They did not report a study funding source. Dr. Ji and coauthors and Dr. Staddon reported no relevant disclosures.
FROM 2021 ASPHO CONFERENCE
No SPARKLE with ibrutinib plus chemo in r/r pediatric B-NHL
Adding ibrutinib to chemotherapy did not improve outcomes for children and young adults with relapsed or refractory mature B-cell non-Hodgkin lymphoma (B-NHL), an interim analysis of the SPARKLE trial showed.
Among 51 patients aged 1-30 years with mature B-NHL that had been diagnosed before age 18, there was no significant difference in the primary endpoint of event-free survival (EFS) between patients assigned on a 2:1 basis to receive either ibrutinib (Imbruvica) plus one of two chemotherapy regimens or to chemotherapy alone. In fact, EFS was shorter among patients assigned to ibrutinib, although a larger proportion of these patients had previously received rituximab, a known factor for poor prognosis, reported Amos Burke, MD, from Cambridge (England) University.
The trial was stopped for futility in May 2020, after a median follow-up of 17.97 months.
“Further studies are required to determine the optimal therapy for patients with relapsed, mature B-NHL, especially those who have received prior rituximab,” he said in an audio walk-through of a scientific poster presented during the annual meeting of the American Society of Pediatric Hematology/Oncology.
“This is a very challenging patient population because they historically have had a very poor survival rate,” commented Paul J. Galardy, MD, a pediatric hematologist/oncologist at the Mayo Clinic in Rochester, Minn., who was not involved in the study.
“The field has struggled to improve outcomes for these patients in part because there are relatively few patients per year with relapsed refractory mature B-cell lymphoma due to the very effective nature of the up-front therapy. This makes new clinical trials difficult to perform,” he said.
Poor prognosis
Ibrutinib, an inhibitor of Bruton tyrosine kinase, is approved in the United States for treatment of marginal zone lymphoma, mantle cell lymphoma, and chronic lymphocytic leukemia/small lymphocytic lymphoma, as well as other indications, all in adults only. It has also been shown to have activity against B-NHL in preclinical and early human trials, Dr. Burke said.
Given the poor prognosis of children and young adults with relapsed/refractory mature B-NHL – a 2-year overall survival (OS) of 30% or less with chemoimmunotherapy – the investigators tested whether adding ibrutinib to the standard of care could improve outcomes.
They enrolled patients with relapsed/refractory B-NHL in first relapse or primarily refractory to conventional therapy, with measurable disease (greater than 1 cm) by CT, bone marrow involvement, or cerebrospinal fluid with blasts. The patients were required to have Karnofsky-Lansky performance scores of 50 or greater.
The histologies included Burkitt lymphoma, diffuse large B-cell lymphoma (DLBCL), Burkitt-like lymphoma, Burkitt leukemia, primary mediastinal B-cell lymphoma, and other unspecified types.
Dr. Burke reported results on 48 patients included in the May 2020 analysis, plus 3 additional patients who were enrolled between the data cutoff for the first analysis and the meeting of the independent data monitoring committee where the decision was made to stop the trial.
A total of 35 patients were randomized to receive ibrutinib with either the RICE (rituximab plus ifosfamide, carboplatin, and etoposide) or RVICI (rituximab plus vincristine, ifosfamide, carboplatin, idarubicin, and dexamethasone) regimen. All of these patients received treatment on study.
Of the 18 patients randomized to receive either RICE or RVICI alone, 1 did not receive any cycles of chemoimmunotherapy.
At the data cutoff for the updated analysis in November 2020, 14 patients assigned to ibrutinib and 4 assigned to chemoimmunotherapy alone remained on study; no patients in either arm were still receiving therapy.
A total of 17 patients assigned to the combination arm died and 4 withdrew consent. In the chemoimmunotherapy-alone arm, 10 died and 2 withdrew consent.
In both arms, patients were treated until either completing three cycles of therapy, start of conditioning treatment prior to stem cell transplantation, disease progression, or unacceptable toxicity.
In the ibrutinib arm, the median EFS was 5.36 months, compared with 6.97 months with chemoimmunotherapy alone, translating into a hazard ratio for EFS with ibrutinib of 1.078 (nonsignificant).
The respective median overall survival was 13.44 versus 11.07 months,
Subgroup analysis showed that EFS and OS did not differ significantly by age, histology, background regimen, or central nervous system or bone marrow involvement.
Overall response rates were 68.6% in the ibrutinib arm, and 81.3% in the chemoimmunotherapy arm. The respective complete response rates were 8.6% and 18.8%, and partial response rates were 60% and 62.5%.
The overall treatment-emergent adverse event (TEAE) profile was similar between the treatment arms, although six patients in the ibrutinib arm versus one in the chemoimmunotherapy arm experienced a major hemorrhage. One patients in the ibrutinib arm died from pulmonary hemorrhage.
Dr. Burke noted that, although the numbers were small, the failure to see a difference in efficacy between study arms may have been caused in part by a greater number of patients assigned to ibrutinib who had received prior treatment with rituximab (85.7% vs. 56.3%).
Not the right partner?
“The results of this study would suggest that ibrutinib is not the right agent. This is not altogether unexpected,” Dr. Galardy said. “The benefit of ibrutinib in adults with mature B-cell lymphoma is primarily based on biological characteristics of lymphomas that develop in older individuals.”
He noted that mature B-cell lymphoma in older adults is often of the activated B-cell subtype, which frequently has mutations that make it sensitive to ibrutinib. In contrast, children, adolescents, and young adults more commonly have the germinal center B-cell subtype that doesn’t have similarly targetable mutations.
He added that, although the reasons for poor prognosis in patients with prior rituximab exposure are unclear, “it is likely that patients who have recurrent or refractory disease after therapy that included rituximab may have developed resistance to this drug. Since both arms of this study included rituximab as a component of the therapy, the patients with prior exposure to this drug may have had reduced benefit of the additional rituximab, compared with those who had not received the drug before.”
The SPARKLE trial was funded by Janssen Research & Development. Dr. Burke disclosed consultancy fees from Janssen and others. Dr. Galardy is an equity holder in Abbott and AbbVie.
Adding ibrutinib to chemotherapy did not improve outcomes for children and young adults with relapsed or refractory mature B-cell non-Hodgkin lymphoma (B-NHL), an interim analysis of the SPARKLE trial showed.
Among 51 patients aged 1-30 years with mature B-NHL that had been diagnosed before age 18, there was no significant difference in the primary endpoint of event-free survival (EFS) between patients assigned on a 2:1 basis to receive either ibrutinib (Imbruvica) plus one of two chemotherapy regimens or to chemotherapy alone. In fact, EFS was shorter among patients assigned to ibrutinib, although a larger proportion of these patients had previously received rituximab, a known factor for poor prognosis, reported Amos Burke, MD, from Cambridge (England) University.
The trial was stopped for futility in May 2020, after a median follow-up of 17.97 months.
“Further studies are required to determine the optimal therapy for patients with relapsed, mature B-NHL, especially those who have received prior rituximab,” he said in an audio walk-through of a scientific poster presented during the annual meeting of the American Society of Pediatric Hematology/Oncology.
“This is a very challenging patient population because they historically have had a very poor survival rate,” commented Paul J. Galardy, MD, a pediatric hematologist/oncologist at the Mayo Clinic in Rochester, Minn., who was not involved in the study.
“The field has struggled to improve outcomes for these patients in part because there are relatively few patients per year with relapsed refractory mature B-cell lymphoma due to the very effective nature of the up-front therapy. This makes new clinical trials difficult to perform,” he said.
Poor prognosis
Ibrutinib, an inhibitor of Bruton tyrosine kinase, is approved in the United States for treatment of marginal zone lymphoma, mantle cell lymphoma, and chronic lymphocytic leukemia/small lymphocytic lymphoma, as well as other indications, all in adults only. It has also been shown to have activity against B-NHL in preclinical and early human trials, Dr. Burke said.
Given the poor prognosis of children and young adults with relapsed/refractory mature B-NHL – a 2-year overall survival (OS) of 30% or less with chemoimmunotherapy – the investigators tested whether adding ibrutinib to the standard of care could improve outcomes.
They enrolled patients with relapsed/refractory B-NHL in first relapse or primarily refractory to conventional therapy, with measurable disease (greater than 1 cm) by CT, bone marrow involvement, or cerebrospinal fluid with blasts. The patients were required to have Karnofsky-Lansky performance scores of 50 or greater.
The histologies included Burkitt lymphoma, diffuse large B-cell lymphoma (DLBCL), Burkitt-like lymphoma, Burkitt leukemia, primary mediastinal B-cell lymphoma, and other unspecified types.
Dr. Burke reported results on 48 patients included in the May 2020 analysis, plus 3 additional patients who were enrolled between the data cutoff for the first analysis and the meeting of the independent data monitoring committee where the decision was made to stop the trial.
A total of 35 patients were randomized to receive ibrutinib with either the RICE (rituximab plus ifosfamide, carboplatin, and etoposide) or RVICI (rituximab plus vincristine, ifosfamide, carboplatin, idarubicin, and dexamethasone) regimen. All of these patients received treatment on study.
Of the 18 patients randomized to receive either RICE or RVICI alone, 1 did not receive any cycles of chemoimmunotherapy.
At the data cutoff for the updated analysis in November 2020, 14 patients assigned to ibrutinib and 4 assigned to chemoimmunotherapy alone remained on study; no patients in either arm were still receiving therapy.
A total of 17 patients assigned to the combination arm died and 4 withdrew consent. In the chemoimmunotherapy-alone arm, 10 died and 2 withdrew consent.
In both arms, patients were treated until either completing three cycles of therapy, start of conditioning treatment prior to stem cell transplantation, disease progression, or unacceptable toxicity.
In the ibrutinib arm, the median EFS was 5.36 months, compared with 6.97 months with chemoimmunotherapy alone, translating into a hazard ratio for EFS with ibrutinib of 1.078 (nonsignificant).
The respective median overall survival was 13.44 versus 11.07 months,
Subgroup analysis showed that EFS and OS did not differ significantly by age, histology, background regimen, or central nervous system or bone marrow involvement.
Overall response rates were 68.6% in the ibrutinib arm, and 81.3% in the chemoimmunotherapy arm. The respective complete response rates were 8.6% and 18.8%, and partial response rates were 60% and 62.5%.
The overall treatment-emergent adverse event (TEAE) profile was similar between the treatment arms, although six patients in the ibrutinib arm versus one in the chemoimmunotherapy arm experienced a major hemorrhage. One patients in the ibrutinib arm died from pulmonary hemorrhage.
Dr. Burke noted that, although the numbers were small, the failure to see a difference in efficacy between study arms may have been caused in part by a greater number of patients assigned to ibrutinib who had received prior treatment with rituximab (85.7% vs. 56.3%).
Not the right partner?
“The results of this study would suggest that ibrutinib is not the right agent. This is not altogether unexpected,” Dr. Galardy said. “The benefit of ibrutinib in adults with mature B-cell lymphoma is primarily based on biological characteristics of lymphomas that develop in older individuals.”
He noted that mature B-cell lymphoma in older adults is often of the activated B-cell subtype, which frequently has mutations that make it sensitive to ibrutinib. In contrast, children, adolescents, and young adults more commonly have the germinal center B-cell subtype that doesn’t have similarly targetable mutations.
He added that, although the reasons for poor prognosis in patients with prior rituximab exposure are unclear, “it is likely that patients who have recurrent or refractory disease after therapy that included rituximab may have developed resistance to this drug. Since both arms of this study included rituximab as a component of the therapy, the patients with prior exposure to this drug may have had reduced benefit of the additional rituximab, compared with those who had not received the drug before.”
The SPARKLE trial was funded by Janssen Research & Development. Dr. Burke disclosed consultancy fees from Janssen and others. Dr. Galardy is an equity holder in Abbott and AbbVie.
Adding ibrutinib to chemotherapy did not improve outcomes for children and young adults with relapsed or refractory mature B-cell non-Hodgkin lymphoma (B-NHL), an interim analysis of the SPARKLE trial showed.
Among 51 patients aged 1-30 years with mature B-NHL that had been diagnosed before age 18, there was no significant difference in the primary endpoint of event-free survival (EFS) between patients assigned on a 2:1 basis to receive either ibrutinib (Imbruvica) plus one of two chemotherapy regimens or to chemotherapy alone. In fact, EFS was shorter among patients assigned to ibrutinib, although a larger proportion of these patients had previously received rituximab, a known factor for poor prognosis, reported Amos Burke, MD, from Cambridge (England) University.
The trial was stopped for futility in May 2020, after a median follow-up of 17.97 months.
“Further studies are required to determine the optimal therapy for patients with relapsed, mature B-NHL, especially those who have received prior rituximab,” he said in an audio walk-through of a scientific poster presented during the annual meeting of the American Society of Pediatric Hematology/Oncology.
“This is a very challenging patient population because they historically have had a very poor survival rate,” commented Paul J. Galardy, MD, a pediatric hematologist/oncologist at the Mayo Clinic in Rochester, Minn., who was not involved in the study.
“The field has struggled to improve outcomes for these patients in part because there are relatively few patients per year with relapsed refractory mature B-cell lymphoma due to the very effective nature of the up-front therapy. This makes new clinical trials difficult to perform,” he said.
Poor prognosis
Ibrutinib, an inhibitor of Bruton tyrosine kinase, is approved in the United States for treatment of marginal zone lymphoma, mantle cell lymphoma, and chronic lymphocytic leukemia/small lymphocytic lymphoma, as well as other indications, all in adults only. It has also been shown to have activity against B-NHL in preclinical and early human trials, Dr. Burke said.
Given the poor prognosis of children and young adults with relapsed/refractory mature B-NHL – a 2-year overall survival (OS) of 30% or less with chemoimmunotherapy – the investigators tested whether adding ibrutinib to the standard of care could improve outcomes.
They enrolled patients with relapsed/refractory B-NHL in first relapse or primarily refractory to conventional therapy, with measurable disease (greater than 1 cm) by CT, bone marrow involvement, or cerebrospinal fluid with blasts. The patients were required to have Karnofsky-Lansky performance scores of 50 or greater.
The histologies included Burkitt lymphoma, diffuse large B-cell lymphoma (DLBCL), Burkitt-like lymphoma, Burkitt leukemia, primary mediastinal B-cell lymphoma, and other unspecified types.
Dr. Burke reported results on 48 patients included in the May 2020 analysis, plus 3 additional patients who were enrolled between the data cutoff for the first analysis and the meeting of the independent data monitoring committee where the decision was made to stop the trial.
A total of 35 patients were randomized to receive ibrutinib with either the RICE (rituximab plus ifosfamide, carboplatin, and etoposide) or RVICI (rituximab plus vincristine, ifosfamide, carboplatin, idarubicin, and dexamethasone) regimen. All of these patients received treatment on study.
Of the 18 patients randomized to receive either RICE or RVICI alone, 1 did not receive any cycles of chemoimmunotherapy.
At the data cutoff for the updated analysis in November 2020, 14 patients assigned to ibrutinib and 4 assigned to chemoimmunotherapy alone remained on study; no patients in either arm were still receiving therapy.
A total of 17 patients assigned to the combination arm died and 4 withdrew consent. In the chemoimmunotherapy-alone arm, 10 died and 2 withdrew consent.
In both arms, patients were treated until either completing three cycles of therapy, start of conditioning treatment prior to stem cell transplantation, disease progression, or unacceptable toxicity.
In the ibrutinib arm, the median EFS was 5.36 months, compared with 6.97 months with chemoimmunotherapy alone, translating into a hazard ratio for EFS with ibrutinib of 1.078 (nonsignificant).
The respective median overall survival was 13.44 versus 11.07 months,
Subgroup analysis showed that EFS and OS did not differ significantly by age, histology, background regimen, or central nervous system or bone marrow involvement.
Overall response rates were 68.6% in the ibrutinib arm, and 81.3% in the chemoimmunotherapy arm. The respective complete response rates were 8.6% and 18.8%, and partial response rates were 60% and 62.5%.
The overall treatment-emergent adverse event (TEAE) profile was similar between the treatment arms, although six patients in the ibrutinib arm versus one in the chemoimmunotherapy arm experienced a major hemorrhage. One patients in the ibrutinib arm died from pulmonary hemorrhage.
Dr. Burke noted that, although the numbers were small, the failure to see a difference in efficacy between study arms may have been caused in part by a greater number of patients assigned to ibrutinib who had received prior treatment with rituximab (85.7% vs. 56.3%).
Not the right partner?
“The results of this study would suggest that ibrutinib is not the right agent. This is not altogether unexpected,” Dr. Galardy said. “The benefit of ibrutinib in adults with mature B-cell lymphoma is primarily based on biological characteristics of lymphomas that develop in older individuals.”
He noted that mature B-cell lymphoma in older adults is often of the activated B-cell subtype, which frequently has mutations that make it sensitive to ibrutinib. In contrast, children, adolescents, and young adults more commonly have the germinal center B-cell subtype that doesn’t have similarly targetable mutations.
He added that, although the reasons for poor prognosis in patients with prior rituximab exposure are unclear, “it is likely that patients who have recurrent or refractory disease after therapy that included rituximab may have developed resistance to this drug. Since both arms of this study included rituximab as a component of the therapy, the patients with prior exposure to this drug may have had reduced benefit of the additional rituximab, compared with those who had not received the drug before.”
The SPARKLE trial was funded by Janssen Research & Development. Dr. Burke disclosed consultancy fees from Janssen and others. Dr. Galardy is an equity holder in Abbott and AbbVie.
FROM ASPHO 2021
High variability found in studies assessing hemophilia-related pain
Chronic pain is a common condition among people with hemophilia and is associated with joint deterioration because of repeated joint bleeds. This systematic review and meta-analysis aimed to determine the prevalence of chronic pain because of hemophilia and to analyze its interference in the lives of patients, according to Ana Cristina Paredes, a PhD student at the University of Minho, Braga, Portugal, and colleagues.
The manuscripts included in the study, which was published online in the Journal of Pain, were mostly observational, cross-sectional studies and one prospective investigation, published between 2009 and 2019.
The issue of pain is particularly important among people with hemophilia, as many adult patients suffer from distinct degrees of arthropathy and associated chronic pain, due to the lifelong occurrence of hemarthrosis, the authors noted. In an important distinction, according to the authors, people with hemophilia may therefore experience both acute pain during bleeds and chronic pain caused by joint deterioration. Acute pain ceases with the resolution of the bleeding episode, but the chronic pain is significantly more challenging, since it persists in time and may trigger changes in the nervous system, leading to peripheral or central sensitization.
Data in the assessed studies were collected from a variety of sources: hemophilia centers, online surveys, by mail, or through a national database, with return rates ranging from 29.2% to 98%. Overall, these studies comprised 4,772 adults, with individual sample sizes ranging from 21 to 2,253 patients, the authors added.
Conflicting results
Overall, there was a widely varying prevalence of hemophilia-related chronic pain reported across studies. Additionally, methodologies and sample characteristics varied widely. The meta-analyses revealed high heterogeneity between studies, and, therefore, pooled prevalence estimates values must be interpreted with caution, the authors stated.
All of the 11 selected studies included for meta-analysis and review reported on the prevalence of chronic pain caused by hemophilia. Chronic pain was assessed using direct questions developed by the authors in eight studies and using the European Haemophilia Therapy Standardization Board definition in three studies. The prevalence for global samples ranged widely from 17% to 84%.
Although there was high heterogeneity, the random-effects meta-analysis including all studies demonstrated a pooled prevalence of 46% of patients reporting chronic pain. Subgroup analyses of studies including all disease severities (mild, moderate, and severe; seven studies) revealed a pooled prevalence of 48%, but also with high heterogeneity. Looking at severe patients only (six studies), the chronic pain prevalence ranged from 33% to 86.4%, with a pooled prevalence of 53% and high heterogeneity, the authors added.
The wide disparity of the chronic pain prevalence seen across the studies is likely because of the fact that some investigations inquired about pain without distinguishing between acute (hemarthrosis-related) or chronic (arthropathy-related) pain, and without clarifying if the only focus is pain caused by hemophilia, or including all causes of pain complaints, according to the researchers.
“Concerning hemophilia-related chronic pain interference, it is striking that the existing literature does not distinguish between the impact of acute or chronic pain. Such a distinction is needed and should be made in future studies to ensure accurate accounts of hemophilia-related pain and to fully understand its interference according to the type of pain (acute vs. chronic). This information is relevant to promote targeted and effective treatment approaches,” the researchers concluded.
The research was supported by a Novo Nordisk HERO Research Grant 2015, the Portuguese Foundation for Science and Technology, and the Foundation for Science and Technology in Portugal. The authors declared they had no conflicts of interest.
Chronic pain is a common condition among people with hemophilia and is associated with joint deterioration because of repeated joint bleeds. This systematic review and meta-analysis aimed to determine the prevalence of chronic pain because of hemophilia and to analyze its interference in the lives of patients, according to Ana Cristina Paredes, a PhD student at the University of Minho, Braga, Portugal, and colleagues.
The manuscripts included in the study, which was published online in the Journal of Pain, were mostly observational, cross-sectional studies and one prospective investigation, published between 2009 and 2019.
The issue of pain is particularly important among people with hemophilia, as many adult patients suffer from distinct degrees of arthropathy and associated chronic pain, due to the lifelong occurrence of hemarthrosis, the authors noted. In an important distinction, according to the authors, people with hemophilia may therefore experience both acute pain during bleeds and chronic pain caused by joint deterioration. Acute pain ceases with the resolution of the bleeding episode, but the chronic pain is significantly more challenging, since it persists in time and may trigger changes in the nervous system, leading to peripheral or central sensitization.
Data in the assessed studies were collected from a variety of sources: hemophilia centers, online surveys, by mail, or through a national database, with return rates ranging from 29.2% to 98%. Overall, these studies comprised 4,772 adults, with individual sample sizes ranging from 21 to 2,253 patients, the authors added.
Conflicting results
Overall, there was a widely varying prevalence of hemophilia-related chronic pain reported across studies. Additionally, methodologies and sample characteristics varied widely. The meta-analyses revealed high heterogeneity between studies, and, therefore, pooled prevalence estimates values must be interpreted with caution, the authors stated.
All of the 11 selected studies included for meta-analysis and review reported on the prevalence of chronic pain caused by hemophilia. Chronic pain was assessed using direct questions developed by the authors in eight studies and using the European Haemophilia Therapy Standardization Board definition in three studies. The prevalence for global samples ranged widely from 17% to 84%.
Although there was high heterogeneity, the random-effects meta-analysis including all studies demonstrated a pooled prevalence of 46% of patients reporting chronic pain. Subgroup analyses of studies including all disease severities (mild, moderate, and severe; seven studies) revealed a pooled prevalence of 48%, but also with high heterogeneity. Looking at severe patients only (six studies), the chronic pain prevalence ranged from 33% to 86.4%, with a pooled prevalence of 53% and high heterogeneity, the authors added.
The wide disparity of the chronic pain prevalence seen across the studies is likely because of the fact that some investigations inquired about pain without distinguishing between acute (hemarthrosis-related) or chronic (arthropathy-related) pain, and without clarifying if the only focus is pain caused by hemophilia, or including all causes of pain complaints, according to the researchers.
“Concerning hemophilia-related chronic pain interference, it is striking that the existing literature does not distinguish between the impact of acute or chronic pain. Such a distinction is needed and should be made in future studies to ensure accurate accounts of hemophilia-related pain and to fully understand its interference according to the type of pain (acute vs. chronic). This information is relevant to promote targeted and effective treatment approaches,” the researchers concluded.
The research was supported by a Novo Nordisk HERO Research Grant 2015, the Portuguese Foundation for Science and Technology, and the Foundation for Science and Technology in Portugal. The authors declared they had no conflicts of interest.
Chronic pain is a common condition among people with hemophilia and is associated with joint deterioration because of repeated joint bleeds. This systematic review and meta-analysis aimed to determine the prevalence of chronic pain because of hemophilia and to analyze its interference in the lives of patients, according to Ana Cristina Paredes, a PhD student at the University of Minho, Braga, Portugal, and colleagues.
The manuscripts included in the study, which was published online in the Journal of Pain, were mostly observational, cross-sectional studies and one prospective investigation, published between 2009 and 2019.
The issue of pain is particularly important among people with hemophilia, as many adult patients suffer from distinct degrees of arthropathy and associated chronic pain, due to the lifelong occurrence of hemarthrosis, the authors noted. In an important distinction, according to the authors, people with hemophilia may therefore experience both acute pain during bleeds and chronic pain caused by joint deterioration. Acute pain ceases with the resolution of the bleeding episode, but the chronic pain is significantly more challenging, since it persists in time and may trigger changes in the nervous system, leading to peripheral or central sensitization.
Data in the assessed studies were collected from a variety of sources: hemophilia centers, online surveys, by mail, or through a national database, with return rates ranging from 29.2% to 98%. Overall, these studies comprised 4,772 adults, with individual sample sizes ranging from 21 to 2,253 patients, the authors added.
Conflicting results
Overall, there was a widely varying prevalence of hemophilia-related chronic pain reported across studies. Additionally, methodologies and sample characteristics varied widely. The meta-analyses revealed high heterogeneity between studies, and, therefore, pooled prevalence estimates values must be interpreted with caution, the authors stated.
All of the 11 selected studies included for meta-analysis and review reported on the prevalence of chronic pain caused by hemophilia. Chronic pain was assessed using direct questions developed by the authors in eight studies and using the European Haemophilia Therapy Standardization Board definition in three studies. The prevalence for global samples ranged widely from 17% to 84%.
Although there was high heterogeneity, the random-effects meta-analysis including all studies demonstrated a pooled prevalence of 46% of patients reporting chronic pain. Subgroup analyses of studies including all disease severities (mild, moderate, and severe; seven studies) revealed a pooled prevalence of 48%, but also with high heterogeneity. Looking at severe patients only (six studies), the chronic pain prevalence ranged from 33% to 86.4%, with a pooled prevalence of 53% and high heterogeneity, the authors added.
The wide disparity of the chronic pain prevalence seen across the studies is likely because of the fact that some investigations inquired about pain without distinguishing between acute (hemarthrosis-related) or chronic (arthropathy-related) pain, and without clarifying if the only focus is pain caused by hemophilia, or including all causes of pain complaints, according to the researchers.
“Concerning hemophilia-related chronic pain interference, it is striking that the existing literature does not distinguish between the impact of acute or chronic pain. Such a distinction is needed and should be made in future studies to ensure accurate accounts of hemophilia-related pain and to fully understand its interference according to the type of pain (acute vs. chronic). This information is relevant to promote targeted and effective treatment approaches,” the researchers concluded.
The research was supported by a Novo Nordisk HERO Research Grant 2015, the Portuguese Foundation for Science and Technology, and the Foundation for Science and Technology in Portugal. The authors declared they had no conflicts of interest.
FROM THE JOURNAL OF PAIN