Jury decides against hospital and surgeon who died by suicide

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Fri, 10/21/2022 - 12:39

The estate of a renowned surgeon is appealing a multimillion-dollar award levied against it and the hospital system he worked foraccording to the New York Post and other news outlets.

In November 2014, New York Giants running back Michael Cox sustained severe lower-body injuries, including a broken leg and a damaged left ankle, after he was tackled in a game against the Seattle Seahawks. At the time, Cox was in the second year of a 4-year, $2.3 million contract with the Giants.

Later, he underwent treatment at New York City’s Hospital for Special Surgery (HSS), the oldest orthopedic hospital in the United States, which is consistently ranked among the best. Mr. Cox’s surgeon for the procedure was Dean Lorich, MD, then associate director of HSS’s orthopedic trauma service and chief of the same service at New York–Presbyterian Hospital, also located in New York City.

But here the story takes a grim turn.

Dr. Lorich’s surgery allegedly failed to fully repair Mr. Cox’s left ankle, which led to the player’s early retirement. In May 2016, Mr. Cox sued Dr. Lorich, HSS, and the New York–Presbyterian Healthcare System for unspecified damages. (Mr. Cox’s attorney at the time reportedly claimed that Dr. Lorich hadn’t properly treated the talus bone in the player’s ankle.) Roughly a year and a half later, in December 2017, police found Dr. Lorich unconscious and unresponsive in his Park Avenue apartment, a knife protruding from his torso. The medical examiner later ruled his death a suicide, though there was no indication of why the surgeon took his own life.

The malpractice suit against Dr. Lorich’s estate and the hospitals continued.

Last month, on September 23, a New York County Supreme Court jury reached its decision. It awarded the ex-NFL player $12 million in lost earnings, $15.5 million for future pain and suffering, and $1 million for past pain and suffering.

“The jury spoke with a clear and unambiguous voice that Mr. Cox received inadequate medical care and treatment and was significantly injured as a result,” announced Jordan Merson, Mr. Cox’s attorney. “We are pleased with the jury’s decision.”

But an attorney for the hospital and the Lorich estate has called the jury verdict “inconsistent with the evidence in the case.” The defendants will appeal the verdict, he says.

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

The content contained in this article is for informational purposes only and does not constitute legal advice. Reliance on any information provided in this article is solely at your own risk.

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The estate of a renowned surgeon is appealing a multimillion-dollar award levied against it and the hospital system he worked foraccording to the New York Post and other news outlets.

In November 2014, New York Giants running back Michael Cox sustained severe lower-body injuries, including a broken leg and a damaged left ankle, after he was tackled in a game against the Seattle Seahawks. At the time, Cox was in the second year of a 4-year, $2.3 million contract with the Giants.

Later, he underwent treatment at New York City’s Hospital for Special Surgery (HSS), the oldest orthopedic hospital in the United States, which is consistently ranked among the best. Mr. Cox’s surgeon for the procedure was Dean Lorich, MD, then associate director of HSS’s orthopedic trauma service and chief of the same service at New York–Presbyterian Hospital, also located in New York City.

But here the story takes a grim turn.

Dr. Lorich’s surgery allegedly failed to fully repair Mr. Cox’s left ankle, which led to the player’s early retirement. In May 2016, Mr. Cox sued Dr. Lorich, HSS, and the New York–Presbyterian Healthcare System for unspecified damages. (Mr. Cox’s attorney at the time reportedly claimed that Dr. Lorich hadn’t properly treated the talus bone in the player’s ankle.) Roughly a year and a half later, in December 2017, police found Dr. Lorich unconscious and unresponsive in his Park Avenue apartment, a knife protruding from his torso. The medical examiner later ruled his death a suicide, though there was no indication of why the surgeon took his own life.

The malpractice suit against Dr. Lorich’s estate and the hospitals continued.

Last month, on September 23, a New York County Supreme Court jury reached its decision. It awarded the ex-NFL player $12 million in lost earnings, $15.5 million for future pain and suffering, and $1 million for past pain and suffering.

“The jury spoke with a clear and unambiguous voice that Mr. Cox received inadequate medical care and treatment and was significantly injured as a result,” announced Jordan Merson, Mr. Cox’s attorney. “We are pleased with the jury’s decision.”

But an attorney for the hospital and the Lorich estate has called the jury verdict “inconsistent with the evidence in the case.” The defendants will appeal the verdict, he says.

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

The content contained in this article is for informational purposes only and does not constitute legal advice. Reliance on any information provided in this article is solely at your own risk.

The estate of a renowned surgeon is appealing a multimillion-dollar award levied against it and the hospital system he worked foraccording to the New York Post and other news outlets.

In November 2014, New York Giants running back Michael Cox sustained severe lower-body injuries, including a broken leg and a damaged left ankle, after he was tackled in a game against the Seattle Seahawks. At the time, Cox was in the second year of a 4-year, $2.3 million contract with the Giants.

Later, he underwent treatment at New York City’s Hospital for Special Surgery (HSS), the oldest orthopedic hospital in the United States, which is consistently ranked among the best. Mr. Cox’s surgeon for the procedure was Dean Lorich, MD, then associate director of HSS’s orthopedic trauma service and chief of the same service at New York–Presbyterian Hospital, also located in New York City.

But here the story takes a grim turn.

Dr. Lorich’s surgery allegedly failed to fully repair Mr. Cox’s left ankle, which led to the player’s early retirement. In May 2016, Mr. Cox sued Dr. Lorich, HSS, and the New York–Presbyterian Healthcare System for unspecified damages. (Mr. Cox’s attorney at the time reportedly claimed that Dr. Lorich hadn’t properly treated the talus bone in the player’s ankle.) Roughly a year and a half later, in December 2017, police found Dr. Lorich unconscious and unresponsive in his Park Avenue apartment, a knife protruding from his torso. The medical examiner later ruled his death a suicide, though there was no indication of why the surgeon took his own life.

The malpractice suit against Dr. Lorich’s estate and the hospitals continued.

Last month, on September 23, a New York County Supreme Court jury reached its decision. It awarded the ex-NFL player $12 million in lost earnings, $15.5 million for future pain and suffering, and $1 million for past pain and suffering.

“The jury spoke with a clear and unambiguous voice that Mr. Cox received inadequate medical care and treatment and was significantly injured as a result,” announced Jordan Merson, Mr. Cox’s attorney. “We are pleased with the jury’s decision.”

But an attorney for the hospital and the Lorich estate has called the jury verdict “inconsistent with the evidence in the case.” The defendants will appeal the verdict, he says.

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

The content contained in this article is for informational purposes only and does not constitute legal advice. Reliance on any information provided in this article is solely at your own risk.

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Global Initiative for Chronic Obstructive Lung Disease guidelines 2022: Management and treatment

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Changed
Fri, 10/28/2022 - 09:37

 

In the United States and around the globe, chronic obstructive pulmonary disease (COPD) remains one of the leading causes of death. In addition to new diagnostic guidelines, the Global Initiative for Chronic Obstructive Lung Disease 2022 Report, or GOLD report, sets forth recommendations for management and treatment. In 2022, a total of 160 new references were added to the previous year’s GOLD report.

According to the GOLD report, initial management of COPD should aim at reducing exposure to risk factors such as smoking or other chemical exposures. In addition to medications, stable COPD patients should be evaluated for inhaler technique, adherence to prescribed therapies, smoking status, and continued exposure to other risk factors. Also, physical activity should be advised and pulmonary rehabilitation should be considered. Spirometry should be performed annually.

Dr. Linda Girgis

These guidelines offer very practical advice but often are difficult to implement in clinical practice. Everyone knows smoking is harmful and quitting provides huge health benefits, not only regarding COPD. However, nicotine is very addictive, and most smokers cannot just quit. Many need smoking cessation aids and counseling. Additionally, some smokers just don’t want to quit. Regarding workplace exposures, it often is not easy for someone just to change their job. Many are afraid to speak because they are afraid of losing their jobs. Everyone, not just patients with COPD, can benefit from increased physical activity, and all doctors know how difficult it is to motivate patients to do this.

The decision to initiate medications should be based on an individual patient’s symptoms and risk of exacerbations. In general, long-acting bronchodilators, including long-acting beta agonists (LABA) and long-acting muscarinic antagonists (LAMA), are preferred except when immediate relief of dyspnea is needed, and then short-acting bronchodilators should be used. Either a single long-acting or dual long-acting bronchodilator can be initiated. If a patient continues to have dyspnea on a single long-acting bronchodilator, treatment should be switched to a dual therapy.

In general, inhaled corticosteroids (ICS) are not recommended for stable COPD patients. If a patient has exacerbations despite appropriate treatment with LABAs, an ICS may be added to the LABA, the GOLD guidelines say. Oral corticosteroids are not recommended for long-term use. PDE4 inhibitors should be considered in patents with severe to very severe airflow obstruction, chronic bronchitis, and exacerbations. Macrolide antibiotics, especially azithromycin, can be considered in acute exacerbations. There is no evidence to support the use of antitussives and mucolytics are advised in only certain patients. Inhaled bronchodilators are advised over oral ones and theophylline is recommended when long-acting bronchodilators are unavailable or unaffordable.

In clinical practice, I see many patients treated based on symptomatology with spirometry testing not being done. This may help control many symptoms, but unless my patient has an accurate diagnosis, I won’t know if my patient is receiving the correct treatment.

It is important to keep in mind that COPD is a progressive disease and without appropriate treatment and monitoring, it will just get worse, and this is most likely to be irreversible.

 

 

Medications and treatment goals for patients with COPD

Patients with alpha-1 antitrypsin deficiency may benefit from the addition of alpha-1 antitrypsin augmentation therapy, the new guidelines say. In patients with severe disease experiencing dyspnea, oral and parental opioids can be considered. Medications that are used to treat primary pulmonary hypertension are not advised to treat pulmonary hypertension secondary to COPD.

The treatment goals of COPD should be to decrease severity of symptoms, reduce the occurrence of exacerbations, and improve exercise tolerance. Peripheral eosinophil counts can be used to guide the use of ICS to prevent exacerbations. However, the best predictor of exacerbations is previous exacerbations. Frequent exacerbations are defined as two or more annually. Additionally, deteriorating airflow is correlated with increased risk of exacerbations, hospitalizations, and death. Forced expiratory volume in 1 second (FEV1) alone lacks precision to predict exacerbations or death.

Vaccines and pulmonary rehabilitation recommended

The Centers for Disease Control and Prevention and World Health Organization recommend several vaccines for stable patients with COPD. Influenza vaccine was shown to reduce serious complications in COPD patients. Pneumococcal vaccines (PCV13 and PPSV23) reduced the likelihood of COPD exacerbations. The COVID-19 vaccine also has been effective at reducing hospitalizations, in particular ICU admissions, and death in patients with COPD. The CDC also recommends TdaP and Zoster vaccines.

An acute exacerbation of COPD occurs when a patient experiences worsening of respiratory symptoms that requires additional treatment, according to the updated GOLD guidelines. They are usually associated with increased airway inflammation, mucous productions, and trapping of gases. They are often triggered by viral infections, but bacterial and environment factors play a role as well. Less commonly, fungi such as Aspergillus can be observed as well. COPD exacerbations contribute to overall progression of the disease.

In patients with hypoxemia, supplemental oxygen should be titrated to a target O2 saturation of 88%-92%. It is important to follow blood gases to be sure adequate oxygenation is taking place while at the same time avoiding carbon dioxide retention and/or worsening acidosis. In patients with severe exacerbations whose dyspnea does not respond to initial emergency therapy, ICU admission is warranted. Other factors indicating the need for ICU admission include mental status changes, persistent or worsening hypoxemia, severe or worsening respiratory acidosis, the need for mechanical ventilation, and hemodynamic instability. Following an acute exacerbation, steps to prevent further exacerbations should be initiated.

Systemic glucocorticoids are indicated during acute exacerbations. They have been shown to hasten recovery time and improve functioning of the lungs as well as oxygenation. It is recommended to give prednisone 40 mg per day for 5 days. Antibiotics should be used in exacerbations if patients have dyspnea, sputum production, and purulence of the sputum or require mechanical ventilation. The choice of which antibiotic to use should be based on local bacterial resistance.

Pulmonary rehabilitation is an important component of COPD management. It incorporates exercise, education, and self-management aimed to change behavior and improve conditioning. The benefits of rehab have been shown to be considerable. The optimal length is 6-8 weeks. Palliative and end-of-life care are also very important factors to consider when treating COPD patients, according to the GOLD guidelines.

COPD is a very common disease and cause of mortality seen by family physicians. The GOLD report is an extensive document providing very clear guidelines and evidence to support these guidelines in every level of the treatment of COPD patients. As primary care doctors, we are often the first to treat patients with COPD and it is important to know the latest guidelines.

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].

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In the United States and around the globe, chronic obstructive pulmonary disease (COPD) remains one of the leading causes of death. In addition to new diagnostic guidelines, the Global Initiative for Chronic Obstructive Lung Disease 2022 Report, or GOLD report, sets forth recommendations for management and treatment. In 2022, a total of 160 new references were added to the previous year’s GOLD report.

According to the GOLD report, initial management of COPD should aim at reducing exposure to risk factors such as smoking or other chemical exposures. In addition to medications, stable COPD patients should be evaluated for inhaler technique, adherence to prescribed therapies, smoking status, and continued exposure to other risk factors. Also, physical activity should be advised and pulmonary rehabilitation should be considered. Spirometry should be performed annually.

Dr. Linda Girgis

These guidelines offer very practical advice but often are difficult to implement in clinical practice. Everyone knows smoking is harmful and quitting provides huge health benefits, not only regarding COPD. However, nicotine is very addictive, and most smokers cannot just quit. Many need smoking cessation aids and counseling. Additionally, some smokers just don’t want to quit. Regarding workplace exposures, it often is not easy for someone just to change their job. Many are afraid to speak because they are afraid of losing their jobs. Everyone, not just patients with COPD, can benefit from increased physical activity, and all doctors know how difficult it is to motivate patients to do this.

The decision to initiate medications should be based on an individual patient’s symptoms and risk of exacerbations. In general, long-acting bronchodilators, including long-acting beta agonists (LABA) and long-acting muscarinic antagonists (LAMA), are preferred except when immediate relief of dyspnea is needed, and then short-acting bronchodilators should be used. Either a single long-acting or dual long-acting bronchodilator can be initiated. If a patient continues to have dyspnea on a single long-acting bronchodilator, treatment should be switched to a dual therapy.

In general, inhaled corticosteroids (ICS) are not recommended for stable COPD patients. If a patient has exacerbations despite appropriate treatment with LABAs, an ICS may be added to the LABA, the GOLD guidelines say. Oral corticosteroids are not recommended for long-term use. PDE4 inhibitors should be considered in patents with severe to very severe airflow obstruction, chronic bronchitis, and exacerbations. Macrolide antibiotics, especially azithromycin, can be considered in acute exacerbations. There is no evidence to support the use of antitussives and mucolytics are advised in only certain patients. Inhaled bronchodilators are advised over oral ones and theophylline is recommended when long-acting bronchodilators are unavailable or unaffordable.

In clinical practice, I see many patients treated based on symptomatology with spirometry testing not being done. This may help control many symptoms, but unless my patient has an accurate diagnosis, I won’t know if my patient is receiving the correct treatment.

It is important to keep in mind that COPD is a progressive disease and without appropriate treatment and monitoring, it will just get worse, and this is most likely to be irreversible.

 

 

Medications and treatment goals for patients with COPD

Patients with alpha-1 antitrypsin deficiency may benefit from the addition of alpha-1 antitrypsin augmentation therapy, the new guidelines say. In patients with severe disease experiencing dyspnea, oral and parental opioids can be considered. Medications that are used to treat primary pulmonary hypertension are not advised to treat pulmonary hypertension secondary to COPD.

The treatment goals of COPD should be to decrease severity of symptoms, reduce the occurrence of exacerbations, and improve exercise tolerance. Peripheral eosinophil counts can be used to guide the use of ICS to prevent exacerbations. However, the best predictor of exacerbations is previous exacerbations. Frequent exacerbations are defined as two or more annually. Additionally, deteriorating airflow is correlated with increased risk of exacerbations, hospitalizations, and death. Forced expiratory volume in 1 second (FEV1) alone lacks precision to predict exacerbations or death.

Vaccines and pulmonary rehabilitation recommended

The Centers for Disease Control and Prevention and World Health Organization recommend several vaccines for stable patients with COPD. Influenza vaccine was shown to reduce serious complications in COPD patients. Pneumococcal vaccines (PCV13 and PPSV23) reduced the likelihood of COPD exacerbations. The COVID-19 vaccine also has been effective at reducing hospitalizations, in particular ICU admissions, and death in patients with COPD. The CDC also recommends TdaP and Zoster vaccines.

An acute exacerbation of COPD occurs when a patient experiences worsening of respiratory symptoms that requires additional treatment, according to the updated GOLD guidelines. They are usually associated with increased airway inflammation, mucous productions, and trapping of gases. They are often triggered by viral infections, but bacterial and environment factors play a role as well. Less commonly, fungi such as Aspergillus can be observed as well. COPD exacerbations contribute to overall progression of the disease.

In patients with hypoxemia, supplemental oxygen should be titrated to a target O2 saturation of 88%-92%. It is important to follow blood gases to be sure adequate oxygenation is taking place while at the same time avoiding carbon dioxide retention and/or worsening acidosis. In patients with severe exacerbations whose dyspnea does not respond to initial emergency therapy, ICU admission is warranted. Other factors indicating the need for ICU admission include mental status changes, persistent or worsening hypoxemia, severe or worsening respiratory acidosis, the need for mechanical ventilation, and hemodynamic instability. Following an acute exacerbation, steps to prevent further exacerbations should be initiated.

Systemic glucocorticoids are indicated during acute exacerbations. They have been shown to hasten recovery time and improve functioning of the lungs as well as oxygenation. It is recommended to give prednisone 40 mg per day for 5 days. Antibiotics should be used in exacerbations if patients have dyspnea, sputum production, and purulence of the sputum or require mechanical ventilation. The choice of which antibiotic to use should be based on local bacterial resistance.

Pulmonary rehabilitation is an important component of COPD management. It incorporates exercise, education, and self-management aimed to change behavior and improve conditioning. The benefits of rehab have been shown to be considerable. The optimal length is 6-8 weeks. Palliative and end-of-life care are also very important factors to consider when treating COPD patients, according to the GOLD guidelines.

COPD is a very common disease and cause of mortality seen by family physicians. The GOLD report is an extensive document providing very clear guidelines and evidence to support these guidelines in every level of the treatment of COPD patients. As primary care doctors, we are often the first to treat patients with COPD and it is important to know the latest guidelines.

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].

 

In the United States and around the globe, chronic obstructive pulmonary disease (COPD) remains one of the leading causes of death. In addition to new diagnostic guidelines, the Global Initiative for Chronic Obstructive Lung Disease 2022 Report, or GOLD report, sets forth recommendations for management and treatment. In 2022, a total of 160 new references were added to the previous year’s GOLD report.

According to the GOLD report, initial management of COPD should aim at reducing exposure to risk factors such as smoking or other chemical exposures. In addition to medications, stable COPD patients should be evaluated for inhaler technique, adherence to prescribed therapies, smoking status, and continued exposure to other risk factors. Also, physical activity should be advised and pulmonary rehabilitation should be considered. Spirometry should be performed annually.

Dr. Linda Girgis

These guidelines offer very practical advice but often are difficult to implement in clinical practice. Everyone knows smoking is harmful and quitting provides huge health benefits, not only regarding COPD. However, nicotine is very addictive, and most smokers cannot just quit. Many need smoking cessation aids and counseling. Additionally, some smokers just don’t want to quit. Regarding workplace exposures, it often is not easy for someone just to change their job. Many are afraid to speak because they are afraid of losing their jobs. Everyone, not just patients with COPD, can benefit from increased physical activity, and all doctors know how difficult it is to motivate patients to do this.

The decision to initiate medications should be based on an individual patient’s symptoms and risk of exacerbations. In general, long-acting bronchodilators, including long-acting beta agonists (LABA) and long-acting muscarinic antagonists (LAMA), are preferred except when immediate relief of dyspnea is needed, and then short-acting bronchodilators should be used. Either a single long-acting or dual long-acting bronchodilator can be initiated. If a patient continues to have dyspnea on a single long-acting bronchodilator, treatment should be switched to a dual therapy.

In general, inhaled corticosteroids (ICS) are not recommended for stable COPD patients. If a patient has exacerbations despite appropriate treatment with LABAs, an ICS may be added to the LABA, the GOLD guidelines say. Oral corticosteroids are not recommended for long-term use. PDE4 inhibitors should be considered in patents with severe to very severe airflow obstruction, chronic bronchitis, and exacerbations. Macrolide antibiotics, especially azithromycin, can be considered in acute exacerbations. There is no evidence to support the use of antitussives and mucolytics are advised in only certain patients. Inhaled bronchodilators are advised over oral ones and theophylline is recommended when long-acting bronchodilators are unavailable or unaffordable.

In clinical practice, I see many patients treated based on symptomatology with spirometry testing not being done. This may help control many symptoms, but unless my patient has an accurate diagnosis, I won’t know if my patient is receiving the correct treatment.

It is important to keep in mind that COPD is a progressive disease and without appropriate treatment and monitoring, it will just get worse, and this is most likely to be irreversible.

 

 

Medications and treatment goals for patients with COPD

Patients with alpha-1 antitrypsin deficiency may benefit from the addition of alpha-1 antitrypsin augmentation therapy, the new guidelines say. In patients with severe disease experiencing dyspnea, oral and parental opioids can be considered. Medications that are used to treat primary pulmonary hypertension are not advised to treat pulmonary hypertension secondary to COPD.

The treatment goals of COPD should be to decrease severity of symptoms, reduce the occurrence of exacerbations, and improve exercise tolerance. Peripheral eosinophil counts can be used to guide the use of ICS to prevent exacerbations. However, the best predictor of exacerbations is previous exacerbations. Frequent exacerbations are defined as two or more annually. Additionally, deteriorating airflow is correlated with increased risk of exacerbations, hospitalizations, and death. Forced expiratory volume in 1 second (FEV1) alone lacks precision to predict exacerbations or death.

Vaccines and pulmonary rehabilitation recommended

The Centers for Disease Control and Prevention and World Health Organization recommend several vaccines for stable patients with COPD. Influenza vaccine was shown to reduce serious complications in COPD patients. Pneumococcal vaccines (PCV13 and PPSV23) reduced the likelihood of COPD exacerbations. The COVID-19 vaccine also has been effective at reducing hospitalizations, in particular ICU admissions, and death in patients with COPD. The CDC also recommends TdaP and Zoster vaccines.

An acute exacerbation of COPD occurs when a patient experiences worsening of respiratory symptoms that requires additional treatment, according to the updated GOLD guidelines. They are usually associated with increased airway inflammation, mucous productions, and trapping of gases. They are often triggered by viral infections, but bacterial and environment factors play a role as well. Less commonly, fungi such as Aspergillus can be observed as well. COPD exacerbations contribute to overall progression of the disease.

In patients with hypoxemia, supplemental oxygen should be titrated to a target O2 saturation of 88%-92%. It is important to follow blood gases to be sure adequate oxygenation is taking place while at the same time avoiding carbon dioxide retention and/or worsening acidosis. In patients with severe exacerbations whose dyspnea does not respond to initial emergency therapy, ICU admission is warranted. Other factors indicating the need for ICU admission include mental status changes, persistent or worsening hypoxemia, severe or worsening respiratory acidosis, the need for mechanical ventilation, and hemodynamic instability. Following an acute exacerbation, steps to prevent further exacerbations should be initiated.

Systemic glucocorticoids are indicated during acute exacerbations. They have been shown to hasten recovery time and improve functioning of the lungs as well as oxygenation. It is recommended to give prednisone 40 mg per day for 5 days. Antibiotics should be used in exacerbations if patients have dyspnea, sputum production, and purulence of the sputum or require mechanical ventilation. The choice of which antibiotic to use should be based on local bacterial resistance.

Pulmonary rehabilitation is an important component of COPD management. It incorporates exercise, education, and self-management aimed to change behavior and improve conditioning. The benefits of rehab have been shown to be considerable. The optimal length is 6-8 weeks. Palliative and end-of-life care are also very important factors to consider when treating COPD patients, according to the GOLD guidelines.

COPD is a very common disease and cause of mortality seen by family physicians. The GOLD report is an extensive document providing very clear guidelines and evidence to support these guidelines in every level of the treatment of COPD patients. As primary care doctors, we are often the first to treat patients with COPD and it is important to know the latest guidelines.

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].

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Hair straighteners’ risk too small for docs to advise against their use

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Thu, 12/15/2022 - 17:16

 

Clarissa Ghazi gets lye relaxers, which contain the chemical sodium hydroxide, applied to her hair two to three times a year.

A recent study that made headlines over a potential link between hair straighteners and uterine cancer is not going to make her stop.

“This study is not enough to cause me to say I’ll stay away from this because [the researchers] don’t prove that using relaxers causes cancer,” Ms. Ghazi said.

Indeed, primary care doctors are unlikely to address the increased risk of uterine cancer in women who frequently use hair straighteners that the study reported.

Among frequent users of hair straighteners – meaning those who used them more than four times a year – the researchers found that women were 2.55 times more likely to be diagnosed with uterine cancer than those who never used these products.

In the recently published paper on this research, the authors said that they found an 80% higher adjusted risk of uterine cancer among women who had ever “straightened,” “relaxed,” or used “hair pressing products” in the 12 months before enrolling in their study.

This finding is “real, but small,” says internist Douglas S. Paauw, MD, professor of medicine at the University of Washington in Seattle.

Dr. Paauw is among several primary care doctors interviewed for this story who expressed little concern about the implications of this research for their patients.

“Since we have hundreds of things we are supposed to discuss at our 20-minute clinic visits, this would not make the cut,” Dr. Paauw said.

While it’s good to be able to answer questions a patient might ask about this new research, the study does not prove anything, he said.

Alan Nelson, MD, an internist-endocrinologist and former special adviser to the CEO of the American College of Physicians, said while the study is well done, the number of actual cases of uterine cancer found was small.

One of the reasons he would not recommend discussing the study with patients is that the brands of hair products used to straighten hair in the study were not identified.

Alexandra White, PhD, lead author of the study, said participants were simply asked, “In the past 12 months, how frequently have you or someone else straightened or relaxed your hair, or used hair pressing products?”

The terms “straightened,” “relaxed,” and “hair pressing products” were not defined, and “some women may have interpreted the term ‘pressing products’ to mean nonchemical products” such as flat irons, Dr. White, head of the National Institute of Environmental Health Sciences’ Environment and Cancer Epidemiology group, said in an email.

Dermatologist Crystal Aguh, MD, associate professor of dermatology at Johns Hopkins University, Baltimore, tweeted the following advice in light of the new findings: “The overall risk of uterine cancer is quite low so it’s important to remember that. For now, if you want to change your routine, there’s no downside to decreasing your frequency of hair straightening to every 12 weeks or more, as that may lessen your risk.”

She also noted that “styles like relaxer, silk pressing, and keratin treatments should only be done by a professional, as this will decrease the likelihood of hair damage and scalp irritation.

“I also encourage women to look for hair products free of parabens and phthalates (which are generically listed as “fragrance”) on products to minimize exposure to hormone disrupting chemicals.”
 

 

 

Not ready to go curly

Ms. Ghazi said she decided to stop using keratin straighteners years ago after she learned they are made with several added ingredients. That includes the chemical formaldehyde, a known carcinogen, according to the American Cancer Society.

“People have been relaxing their hair for a very long time, and I feel more comfortable using [a relaxer] to straighten my hair than any of the others out there,” Ms. Ghazi said.

Janaki Ram, who has had her hair chemically straightened several times, said the findings have not made her worried that straightening will cause her to get uterine cancer specifically, but that they are a reminder that the chemicals in these products could harm her in some other way.

She said the new study findings, her knowledge of the damage straightening causes to hair, and the lengthy amount of time receiving a keratin treatment takes will lead her to reduce the frequency with which she gets her hair straightened.

“Going forward, I will have this done once a year instead of twice a year,” she said.

Dr. White, the author of the paper, said in an interview that the takeaway for consumers is that women who reported frequent use of hair straighteners/relaxers and pressing products were more than twice as likely to go on to develop uterine cancer compared to women who reported no use of these products in the previous year.

“However, uterine cancer is relatively rare, so these increases in risks are small,” she said. “Less frequent use of these products was not as strongly associated with risk, suggesting that decreasing use may be an option to reduce harmful exposure. Black women were the most frequent users of these products and therefore these findings are more relevant for Black women.”

In a statement, Dr. White noted, “We estimated that 1.64% of women who never used hair straighteners would go on to develop uterine cancer by the age of 70; but for frequent users, that risk goes up to 4.05%.”

The findings were based on the Sister Study, which enrolled women living in the United States, including Puerto Rico, between 2003 and 2009. Participants needed to have at least one sister who had been diagnosed with breast cancer, been breast cancer-free themselves, and aged 35-74 years. Women who reported a diagnosis of uterine cancer before enrollment, had an uncertain uterine cancer history, or had a hysterectomy were excluded from the study.

The researchers examined hair product usage and uterine cancer incidence during an 11-year period among 33 ,947 women. The analysis controlled for variables such as age, race, and risk factors. At baseline, participants were asked to complete a questionnaire on hair products use in the previous 12 months.

“One of the original aims of the study was to better understand the environmental and genetic causes of breast cancer, but we are also interested in studying ovarian cancer, uterine cancer, and many other cancers and chronic diseases,” Dr. White said.

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

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Clarissa Ghazi gets lye relaxers, which contain the chemical sodium hydroxide, applied to her hair two to three times a year.

A recent study that made headlines over a potential link between hair straighteners and uterine cancer is not going to make her stop.

“This study is not enough to cause me to say I’ll stay away from this because [the researchers] don’t prove that using relaxers causes cancer,” Ms. Ghazi said.

Indeed, primary care doctors are unlikely to address the increased risk of uterine cancer in women who frequently use hair straighteners that the study reported.

Among frequent users of hair straighteners – meaning those who used them more than four times a year – the researchers found that women were 2.55 times more likely to be diagnosed with uterine cancer than those who never used these products.

In the recently published paper on this research, the authors said that they found an 80% higher adjusted risk of uterine cancer among women who had ever “straightened,” “relaxed,” or used “hair pressing products” in the 12 months before enrolling in their study.

This finding is “real, but small,” says internist Douglas S. Paauw, MD, professor of medicine at the University of Washington in Seattle.

Dr. Paauw is among several primary care doctors interviewed for this story who expressed little concern about the implications of this research for their patients.

“Since we have hundreds of things we are supposed to discuss at our 20-minute clinic visits, this would not make the cut,” Dr. Paauw said.

While it’s good to be able to answer questions a patient might ask about this new research, the study does not prove anything, he said.

Alan Nelson, MD, an internist-endocrinologist and former special adviser to the CEO of the American College of Physicians, said while the study is well done, the number of actual cases of uterine cancer found was small.

One of the reasons he would not recommend discussing the study with patients is that the brands of hair products used to straighten hair in the study were not identified.

Alexandra White, PhD, lead author of the study, said participants were simply asked, “In the past 12 months, how frequently have you or someone else straightened or relaxed your hair, or used hair pressing products?”

The terms “straightened,” “relaxed,” and “hair pressing products” were not defined, and “some women may have interpreted the term ‘pressing products’ to mean nonchemical products” such as flat irons, Dr. White, head of the National Institute of Environmental Health Sciences’ Environment and Cancer Epidemiology group, said in an email.

Dermatologist Crystal Aguh, MD, associate professor of dermatology at Johns Hopkins University, Baltimore, tweeted the following advice in light of the new findings: “The overall risk of uterine cancer is quite low so it’s important to remember that. For now, if you want to change your routine, there’s no downside to decreasing your frequency of hair straightening to every 12 weeks or more, as that may lessen your risk.”

She also noted that “styles like relaxer, silk pressing, and keratin treatments should only be done by a professional, as this will decrease the likelihood of hair damage and scalp irritation.

“I also encourage women to look for hair products free of parabens and phthalates (which are generically listed as “fragrance”) on products to minimize exposure to hormone disrupting chemicals.”
 

 

 

Not ready to go curly

Ms. Ghazi said she decided to stop using keratin straighteners years ago after she learned they are made with several added ingredients. That includes the chemical formaldehyde, a known carcinogen, according to the American Cancer Society.

“People have been relaxing their hair for a very long time, and I feel more comfortable using [a relaxer] to straighten my hair than any of the others out there,” Ms. Ghazi said.

Janaki Ram, who has had her hair chemically straightened several times, said the findings have not made her worried that straightening will cause her to get uterine cancer specifically, but that they are a reminder that the chemicals in these products could harm her in some other way.

She said the new study findings, her knowledge of the damage straightening causes to hair, and the lengthy amount of time receiving a keratin treatment takes will lead her to reduce the frequency with which she gets her hair straightened.

“Going forward, I will have this done once a year instead of twice a year,” she said.

Dr. White, the author of the paper, said in an interview that the takeaway for consumers is that women who reported frequent use of hair straighteners/relaxers and pressing products were more than twice as likely to go on to develop uterine cancer compared to women who reported no use of these products in the previous year.

“However, uterine cancer is relatively rare, so these increases in risks are small,” she said. “Less frequent use of these products was not as strongly associated with risk, suggesting that decreasing use may be an option to reduce harmful exposure. Black women were the most frequent users of these products and therefore these findings are more relevant for Black women.”

In a statement, Dr. White noted, “We estimated that 1.64% of women who never used hair straighteners would go on to develop uterine cancer by the age of 70; but for frequent users, that risk goes up to 4.05%.”

The findings were based on the Sister Study, which enrolled women living in the United States, including Puerto Rico, between 2003 and 2009. Participants needed to have at least one sister who had been diagnosed with breast cancer, been breast cancer-free themselves, and aged 35-74 years. Women who reported a diagnosis of uterine cancer before enrollment, had an uncertain uterine cancer history, or had a hysterectomy were excluded from the study.

The researchers examined hair product usage and uterine cancer incidence during an 11-year period among 33 ,947 women. The analysis controlled for variables such as age, race, and risk factors. At baseline, participants were asked to complete a questionnaire on hair products use in the previous 12 months.

“One of the original aims of the study was to better understand the environmental and genetic causes of breast cancer, but we are also interested in studying ovarian cancer, uterine cancer, and many other cancers and chronic diseases,” Dr. White said.

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

 

Clarissa Ghazi gets lye relaxers, which contain the chemical sodium hydroxide, applied to her hair two to three times a year.

A recent study that made headlines over a potential link between hair straighteners and uterine cancer is not going to make her stop.

“This study is not enough to cause me to say I’ll stay away from this because [the researchers] don’t prove that using relaxers causes cancer,” Ms. Ghazi said.

Indeed, primary care doctors are unlikely to address the increased risk of uterine cancer in women who frequently use hair straighteners that the study reported.

Among frequent users of hair straighteners – meaning those who used them more than four times a year – the researchers found that women were 2.55 times more likely to be diagnosed with uterine cancer than those who never used these products.

In the recently published paper on this research, the authors said that they found an 80% higher adjusted risk of uterine cancer among women who had ever “straightened,” “relaxed,” or used “hair pressing products” in the 12 months before enrolling in their study.

This finding is “real, but small,” says internist Douglas S. Paauw, MD, professor of medicine at the University of Washington in Seattle.

Dr. Paauw is among several primary care doctors interviewed for this story who expressed little concern about the implications of this research for their patients.

“Since we have hundreds of things we are supposed to discuss at our 20-minute clinic visits, this would not make the cut,” Dr. Paauw said.

While it’s good to be able to answer questions a patient might ask about this new research, the study does not prove anything, he said.

Alan Nelson, MD, an internist-endocrinologist and former special adviser to the CEO of the American College of Physicians, said while the study is well done, the number of actual cases of uterine cancer found was small.

One of the reasons he would not recommend discussing the study with patients is that the brands of hair products used to straighten hair in the study were not identified.

Alexandra White, PhD, lead author of the study, said participants were simply asked, “In the past 12 months, how frequently have you or someone else straightened or relaxed your hair, or used hair pressing products?”

The terms “straightened,” “relaxed,” and “hair pressing products” were not defined, and “some women may have interpreted the term ‘pressing products’ to mean nonchemical products” such as flat irons, Dr. White, head of the National Institute of Environmental Health Sciences’ Environment and Cancer Epidemiology group, said in an email.

Dermatologist Crystal Aguh, MD, associate professor of dermatology at Johns Hopkins University, Baltimore, tweeted the following advice in light of the new findings: “The overall risk of uterine cancer is quite low so it’s important to remember that. For now, if you want to change your routine, there’s no downside to decreasing your frequency of hair straightening to every 12 weeks or more, as that may lessen your risk.”

She also noted that “styles like relaxer, silk pressing, and keratin treatments should only be done by a professional, as this will decrease the likelihood of hair damage and scalp irritation.

“I also encourage women to look for hair products free of parabens and phthalates (which are generically listed as “fragrance”) on products to minimize exposure to hormone disrupting chemicals.”
 

 

 

Not ready to go curly

Ms. Ghazi said she decided to stop using keratin straighteners years ago after she learned they are made with several added ingredients. That includes the chemical formaldehyde, a known carcinogen, according to the American Cancer Society.

“People have been relaxing their hair for a very long time, and I feel more comfortable using [a relaxer] to straighten my hair than any of the others out there,” Ms. Ghazi said.

Janaki Ram, who has had her hair chemically straightened several times, said the findings have not made her worried that straightening will cause her to get uterine cancer specifically, but that they are a reminder that the chemicals in these products could harm her in some other way.

She said the new study findings, her knowledge of the damage straightening causes to hair, and the lengthy amount of time receiving a keratin treatment takes will lead her to reduce the frequency with which she gets her hair straightened.

“Going forward, I will have this done once a year instead of twice a year,” she said.

Dr. White, the author of the paper, said in an interview that the takeaway for consumers is that women who reported frequent use of hair straighteners/relaxers and pressing products were more than twice as likely to go on to develop uterine cancer compared to women who reported no use of these products in the previous year.

“However, uterine cancer is relatively rare, so these increases in risks are small,” she said. “Less frequent use of these products was not as strongly associated with risk, suggesting that decreasing use may be an option to reduce harmful exposure. Black women were the most frequent users of these products and therefore these findings are more relevant for Black women.”

In a statement, Dr. White noted, “We estimated that 1.64% of women who never used hair straighteners would go on to develop uterine cancer by the age of 70; but for frequent users, that risk goes up to 4.05%.”

The findings were based on the Sister Study, which enrolled women living in the United States, including Puerto Rico, between 2003 and 2009. Participants needed to have at least one sister who had been diagnosed with breast cancer, been breast cancer-free themselves, and aged 35-74 years. Women who reported a diagnosis of uterine cancer before enrollment, had an uncertain uterine cancer history, or had a hysterectomy were excluded from the study.

The researchers examined hair product usage and uterine cancer incidence during an 11-year period among 33 ,947 women. The analysis controlled for variables such as age, race, and risk factors. At baseline, participants were asked to complete a questionnaire on hair products use in the previous 12 months.

“One of the original aims of the study was to better understand the environmental and genetic causes of breast cancer, but we are also interested in studying ovarian cancer, uterine cancer, and many other cancers and chronic diseases,” Dr. White said.

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

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AGA President Dr. John Carethers named vice chancellor at UCSD

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Fri, 10/21/2022 - 09:44

Everyone at AGA sends our congratulations to AGA President John Carethers, MD, AGAF, on his appointment as the vice chancellor for health sciences at the University of California San Diego.

Dr. Carethers, who began his term as the 117th president of the AGA Institute on June 1, 2022, is returning to UC San Diego after a 13-year tenure at the University of Michigan. He will report directly to the chancellor and serve as a part of the leadership team, effective Jan. 1, 2023.

Aside from his new role at UCSD, Dr. Carethers has been an active member of AGA for more than 20 years and has served on several AGA committees, including the AGA Nominating Committee, AGA Underrepresented Minorities Committee, AGA Research Policy Committee, AGA Institute Council and the AGA Trainee & Young GI Committee.

We wish him well in this new chapter!

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Everyone at AGA sends our congratulations to AGA President John Carethers, MD, AGAF, on his appointment as the vice chancellor for health sciences at the University of California San Diego.

Dr. Carethers, who began his term as the 117th president of the AGA Institute on June 1, 2022, is returning to UC San Diego after a 13-year tenure at the University of Michigan. He will report directly to the chancellor and serve as a part of the leadership team, effective Jan. 1, 2023.

Aside from his new role at UCSD, Dr. Carethers has been an active member of AGA for more than 20 years and has served on several AGA committees, including the AGA Nominating Committee, AGA Underrepresented Minorities Committee, AGA Research Policy Committee, AGA Institute Council and the AGA Trainee & Young GI Committee.

We wish him well in this new chapter!

Everyone at AGA sends our congratulations to AGA President John Carethers, MD, AGAF, on his appointment as the vice chancellor for health sciences at the University of California San Diego.

Dr. Carethers, who began his term as the 117th president of the AGA Institute on June 1, 2022, is returning to UC San Diego after a 13-year tenure at the University of Michigan. He will report directly to the chancellor and serve as a part of the leadership team, effective Jan. 1, 2023.

Aside from his new role at UCSD, Dr. Carethers has been an active member of AGA for more than 20 years and has served on several AGA committees, including the AGA Nominating Committee, AGA Underrepresented Minorities Committee, AGA Research Policy Committee, AGA Institute Council and the AGA Trainee & Young GI Committee.

We wish him well in this new chapter!

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Germline genetic testing: Why it matters and where we are failing

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Fri, 10/21/2022 - 09:27

 

Historically, the role of genetic testing has been to identify familial cancer syndromes and initiate cascade testing. If a germline pathogenic variant is found in an individual, cascade testing involves genetic counseling and testing of blood relatives, starting with those closest in relation to the proband, to identify other family members at high hereditary cancer risk. Once testing identifies those family members at higher cancer risk, these individuals can be referred for risk-reducing procedures. They can undergo screening tests starting at an earlier age and/or increased frequency to help prevent invasive cancer or diagnose it at an earlier stage.

Genetic testing can also inform prognosis. While women with a BRCA1 or BRCA2 mutation are at higher risk of developing ovarian cancer compared with the baseline population, the presence of a germline BRCA mutation has been shown to confer improved survival compared with no BRCA mutation (BRCA wild type). However, more recent data have shown that when long-term survival was analyzed, the prognostic benefit seen in patients with a germline BRCA mutation was lost. The initial survival advantage seen in this population may be related to increased sensitivity to treatment. There appears to be improved response to platinum therapy, which is the standard of care for upfront treatment, in germline BRCA mutation carriers.

Dr. Katherine Tucker

Most recently, genetic testing has been used to guide treatment decisions in gynecologic cancers. In 2014, the first poly ADP-ribose polymerase (PARP) inhibitor, olaparib, received Food and Drug Administration approval for the treatment of recurrent ovarian cancer in the presence of a germline BRCA mutation. Now there are multiple PARP inhibitors that have FDA approval for ovarian cancer treatment, some as frontline treatment.

Previous data indicate that 13%-18% of women with ovarian cancer have a germline BRCA mutation that places them at increased risk of hereditary ovarian cancer.1 Current guidelines from the American Society of Clinical Oncology, the U.S. Preventive Services Task Force, the National Comprehensive Cancer Network, the Society of Gynecologic Oncology (SGO), and the American College of Obstetricians and Gynecologists recommend universal genetic counseling and testing for patients diagnosed with epithelial ovarian cancer. Despite these guidelines, rates of referral for genetic counseling and completion of genetic testing are low.

There has been improvement for both referrals and testing since the publication of the 2014 SGO clinical practice statement on genetic testing for ovarian cancer patients, which recommended that all women, even those without any significant family history, should receive genetic counseling and be offered genetic testing.2 When including only studies that collected data after the publication of the 2014 SGO clinical practice statement on genetic testing, a recent systematic review found that 64% of patients were referred for genetic counseling and 63% underwent testing.3

Clinical interventions to target genetic evaluation appear to improve uptake of both counseling and testing. These interventions include using telemedicine to deliver genetic counseling services, mainstreaming (counseling and testing are provided in an oncology clinic by nongenetics specialists), having a genetic counselor within the clinic, and performing reflex testing. With limited numbers of genetic counselors (and even further limited numbers of cancer-specific genetic counselors),4 referral for genetic counseling before testing is often challenging and may not be feasible. There is continued need for strategies to help overcome the barrier to accessing genetic counseling.

While the data are limited, there appear to be significant disparities in rates of genetic testing. Genetic counseling and testing were completed by White (43% and 40%) patients more frequently than by either Black (24% and 26%) or Asian (23% and 14%) patients.4 Uninsured patients were about half as likely (23% vs. 47%) to complete genetic testing as were those with private insurance.4

Genetic testing is an important tool to help identify individuals and families at risk of having hereditary cancer syndromes. This identification allows us to prevent many cancers and identify others while still early stage, significantly decreasing the health care and financial burden on our society and improving outcomes for patients. While we have seen improvement in rates of referral for genetic counseling and testing, we are still falling short. Given the shortage of genetic counselors, it is imperative that we find solutions to ensure continued and improved access to genetic testing for our patients.
 

Dr. Tucker is assistant professor of gynecologic oncology at the University of North Carolina at Chapel Hill.

References

1. Norquist BM et al. JAMA Oncol. 2016;2(4):482-90.

2. SGO Clinical Practice Statement. 2014 Oct 1.

3. Lin J et al. Gynecol Oncol. 2021;162(2):506-16.

4. American Society of Clinical Oncology. J Oncol Pract. 2016 Apr;12(4):339-83.

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Historically, the role of genetic testing has been to identify familial cancer syndromes and initiate cascade testing. If a germline pathogenic variant is found in an individual, cascade testing involves genetic counseling and testing of blood relatives, starting with those closest in relation to the proband, to identify other family members at high hereditary cancer risk. Once testing identifies those family members at higher cancer risk, these individuals can be referred for risk-reducing procedures. They can undergo screening tests starting at an earlier age and/or increased frequency to help prevent invasive cancer or diagnose it at an earlier stage.

Genetic testing can also inform prognosis. While women with a BRCA1 or BRCA2 mutation are at higher risk of developing ovarian cancer compared with the baseline population, the presence of a germline BRCA mutation has been shown to confer improved survival compared with no BRCA mutation (BRCA wild type). However, more recent data have shown that when long-term survival was analyzed, the prognostic benefit seen in patients with a germline BRCA mutation was lost. The initial survival advantage seen in this population may be related to increased sensitivity to treatment. There appears to be improved response to platinum therapy, which is the standard of care for upfront treatment, in germline BRCA mutation carriers.

Dr. Katherine Tucker

Most recently, genetic testing has been used to guide treatment decisions in gynecologic cancers. In 2014, the first poly ADP-ribose polymerase (PARP) inhibitor, olaparib, received Food and Drug Administration approval for the treatment of recurrent ovarian cancer in the presence of a germline BRCA mutation. Now there are multiple PARP inhibitors that have FDA approval for ovarian cancer treatment, some as frontline treatment.

Previous data indicate that 13%-18% of women with ovarian cancer have a germline BRCA mutation that places them at increased risk of hereditary ovarian cancer.1 Current guidelines from the American Society of Clinical Oncology, the U.S. Preventive Services Task Force, the National Comprehensive Cancer Network, the Society of Gynecologic Oncology (SGO), and the American College of Obstetricians and Gynecologists recommend universal genetic counseling and testing for patients diagnosed with epithelial ovarian cancer. Despite these guidelines, rates of referral for genetic counseling and completion of genetic testing are low.

There has been improvement for both referrals and testing since the publication of the 2014 SGO clinical practice statement on genetic testing for ovarian cancer patients, which recommended that all women, even those without any significant family history, should receive genetic counseling and be offered genetic testing.2 When including only studies that collected data after the publication of the 2014 SGO clinical practice statement on genetic testing, a recent systematic review found that 64% of patients were referred for genetic counseling and 63% underwent testing.3

Clinical interventions to target genetic evaluation appear to improve uptake of both counseling and testing. These interventions include using telemedicine to deliver genetic counseling services, mainstreaming (counseling and testing are provided in an oncology clinic by nongenetics specialists), having a genetic counselor within the clinic, and performing reflex testing. With limited numbers of genetic counselors (and even further limited numbers of cancer-specific genetic counselors),4 referral for genetic counseling before testing is often challenging and may not be feasible. There is continued need for strategies to help overcome the barrier to accessing genetic counseling.

While the data are limited, there appear to be significant disparities in rates of genetic testing. Genetic counseling and testing were completed by White (43% and 40%) patients more frequently than by either Black (24% and 26%) or Asian (23% and 14%) patients.4 Uninsured patients were about half as likely (23% vs. 47%) to complete genetic testing as were those with private insurance.4

Genetic testing is an important tool to help identify individuals and families at risk of having hereditary cancer syndromes. This identification allows us to prevent many cancers and identify others while still early stage, significantly decreasing the health care and financial burden on our society and improving outcomes for patients. While we have seen improvement in rates of referral for genetic counseling and testing, we are still falling short. Given the shortage of genetic counselors, it is imperative that we find solutions to ensure continued and improved access to genetic testing for our patients.
 

Dr. Tucker is assistant professor of gynecologic oncology at the University of North Carolina at Chapel Hill.

References

1. Norquist BM et al. JAMA Oncol. 2016;2(4):482-90.

2. SGO Clinical Practice Statement. 2014 Oct 1.

3. Lin J et al. Gynecol Oncol. 2021;162(2):506-16.

4. American Society of Clinical Oncology. J Oncol Pract. 2016 Apr;12(4):339-83.

 

Historically, the role of genetic testing has been to identify familial cancer syndromes and initiate cascade testing. If a germline pathogenic variant is found in an individual, cascade testing involves genetic counseling and testing of blood relatives, starting with those closest in relation to the proband, to identify other family members at high hereditary cancer risk. Once testing identifies those family members at higher cancer risk, these individuals can be referred for risk-reducing procedures. They can undergo screening tests starting at an earlier age and/or increased frequency to help prevent invasive cancer or diagnose it at an earlier stage.

Genetic testing can also inform prognosis. While women with a BRCA1 or BRCA2 mutation are at higher risk of developing ovarian cancer compared with the baseline population, the presence of a germline BRCA mutation has been shown to confer improved survival compared with no BRCA mutation (BRCA wild type). However, more recent data have shown that when long-term survival was analyzed, the prognostic benefit seen in patients with a germline BRCA mutation was lost. The initial survival advantage seen in this population may be related to increased sensitivity to treatment. There appears to be improved response to platinum therapy, which is the standard of care for upfront treatment, in germline BRCA mutation carriers.

Dr. Katherine Tucker

Most recently, genetic testing has been used to guide treatment decisions in gynecologic cancers. In 2014, the first poly ADP-ribose polymerase (PARP) inhibitor, olaparib, received Food and Drug Administration approval for the treatment of recurrent ovarian cancer in the presence of a germline BRCA mutation. Now there are multiple PARP inhibitors that have FDA approval for ovarian cancer treatment, some as frontline treatment.

Previous data indicate that 13%-18% of women with ovarian cancer have a germline BRCA mutation that places them at increased risk of hereditary ovarian cancer.1 Current guidelines from the American Society of Clinical Oncology, the U.S. Preventive Services Task Force, the National Comprehensive Cancer Network, the Society of Gynecologic Oncology (SGO), and the American College of Obstetricians and Gynecologists recommend universal genetic counseling and testing for patients diagnosed with epithelial ovarian cancer. Despite these guidelines, rates of referral for genetic counseling and completion of genetic testing are low.

There has been improvement for both referrals and testing since the publication of the 2014 SGO clinical practice statement on genetic testing for ovarian cancer patients, which recommended that all women, even those without any significant family history, should receive genetic counseling and be offered genetic testing.2 When including only studies that collected data after the publication of the 2014 SGO clinical practice statement on genetic testing, a recent systematic review found that 64% of patients were referred for genetic counseling and 63% underwent testing.3

Clinical interventions to target genetic evaluation appear to improve uptake of both counseling and testing. These interventions include using telemedicine to deliver genetic counseling services, mainstreaming (counseling and testing are provided in an oncology clinic by nongenetics specialists), having a genetic counselor within the clinic, and performing reflex testing. With limited numbers of genetic counselors (and even further limited numbers of cancer-specific genetic counselors),4 referral for genetic counseling before testing is often challenging and may not be feasible. There is continued need for strategies to help overcome the barrier to accessing genetic counseling.

While the data are limited, there appear to be significant disparities in rates of genetic testing. Genetic counseling and testing were completed by White (43% and 40%) patients more frequently than by either Black (24% and 26%) or Asian (23% and 14%) patients.4 Uninsured patients were about half as likely (23% vs. 47%) to complete genetic testing as were those with private insurance.4

Genetic testing is an important tool to help identify individuals and families at risk of having hereditary cancer syndromes. This identification allows us to prevent many cancers and identify others while still early stage, significantly decreasing the health care and financial burden on our society and improving outcomes for patients. While we have seen improvement in rates of referral for genetic counseling and testing, we are still falling short. Given the shortage of genetic counselors, it is imperative that we find solutions to ensure continued and improved access to genetic testing for our patients.
 

Dr. Tucker is assistant professor of gynecologic oncology at the University of North Carolina at Chapel Hill.

References

1. Norquist BM et al. JAMA Oncol. 2016;2(4):482-90.

2. SGO Clinical Practice Statement. 2014 Oct 1.

3. Lin J et al. Gynecol Oncol. 2021;162(2):506-16.

4. American Society of Clinical Oncology. J Oncol Pract. 2016 Apr;12(4):339-83.

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Ten-day methotrexate pause after COVID vaccine booster enhances immunity against Omicron variant

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Tue, 02/07/2023 - 16:38

People taking methotrexate for immunomodulatory diseases can skip one or two scheduled doses after they get an mRNA-based vaccine booster for COVID-19 and achieve a level of immunity against Omicron variants that’s comparable to people who aren’t immunosuppressed, a small observational cohort study from Germany reported.

Kmatta/Moment/Getty Images

“In general, the data suggest that pausing methotrexate is feasible, and it’s sufficient if the last dose occurs 1-3 days before the vaccination,” study coauthor Gerd Burmester, MD, a senior professor of rheumatology and immunology at the University of Medicine Berlin, told this news organization. “In pragmatic terms: pausing the methotrexate injection just twice after the vaccine is finished and, interestingly, not prior to the vaccination.”

Dr. Gerd Burmester


The study, published online in RMD Open, included a statistical analysis that determined that a 10-day pause after the vaccination would be optimal, Dr. Burmester said.

Dr. Burmester and coauthors claimed this is the first study to evaluate the antibody response in patients on methotrexate against Omicron variants – in this study, variants BA.1 and BA.2 – after getting a COVID-19 mRNA booster. The study compared neutralizing serum activity of 50 patients taking methotrexate – 24 of whom continued treatments uninterrupted and 26 of whom paused treatments after getting a second booster – with 25 nonimmunosuppressed patients who served as controls. A total of 24% of the patients taking methotrexate received the mRNA-1273 vaccine while the entire control group received the Pfizer/BioNTech BNT162b2 vaccine.

The researchers used SARS-CoV-2 pseudovirus neutralization assays to evaluate post-vaccination antibody levels.

The U.S. Centers for Disease Control and Prevention and other government health agencies have recommended that immunocompromised patients get a fourth COVID-19 vaccination. But these vaccines can be problematic in patients taking methotrexate, which was linked to a reduced response after the second and third doses of the COVID-19 vaccine.

Previous studies reported that pausing methotrexate for 10 or 14 days after the first two vaccinations improved the production of neutralizing antibodies. A 2022 study found that a 2-week pause after a booster increased antibody response against S1 RBD (receptor binding domain) of the SARS-CoV-2 spike protein about twofold. Another recently published study of mRNA vaccines found that taking methotrexate with either a biologic or targeted synthetic disease-modifying antirheumatic drug reduces the efficacy of a third (booster) shot of SARS-CoV-2 mRNA vaccine in older adults but not younger patients with RA.

“Our study and also the other studies suggested that you can pause methotrexate treatment safely from a point of view of disease activity of rheumatoid arthritis,” Dr. Burmester said. “If you do the pause just twice or once only, it doesn’t lead to significant flares.”
 

Study results

The study found that serum neutralizing activity against the Omicron BA.1 variant, measured as geometric mean 50% inhibitory serum dilution (ID50s), wasn’t significantly different between the methotrexate and the nonimmunosuppressed groups before getting their mRNA booster (P = .657). However, 4 weeks after getting the booster, the nonimmunosuppressed group had a 68-fold increase in antibody activity versus a 20-fold increase in the methotrexate patients. After 12 weeks, ID50s in both groups decreased by about half (P = .001).

 

 

The methotrexate patients who continued therapy after the booster had significantly lower neutralization against Omicron BA.1 at both 4 weeks and 12 weeks than did their counterparts who paused therapy, as well as control patients.

The results were very similar in the same group comparisons of the serum neutralizing activity against the Omicron BA.2 variant at 4 and 12 weeks after booster vaccination.
 

Expert commentary

This study is noteworthy because it used SARS-CoV-2 pseudovirus neutralization assays to evaluate antibody levels, Kevin Winthrop, MD, MPH, professor of infectious disease and public health at Oregon Health & Science University, Portland, who was not involved in the study, said. “A lot of studies don’t look at neutralizing antibody titers, and that’s really what we care about,” Dr. Winthrop said. “What we want are functional antibodies that are doing something, and the only way to do that is to test them.”

Dr. Kevin Winthrop

The study is “confirmatory” of other studies that call for pausing methotrexate after vaccination, Dr. Winthrop said, including a study he coauthored, and which the German researchers cited, that found pausing methotrexate for a week or so after the influenza vaccination in RA patients improved vaccine immunogenicity. He added that the findings with the early Omicron variants are important because the newest boosters target the later Omicron variants, BA.4 and BA.5.

“The bottom line is that when someone comes in for a COVID-19 vaccination, tell them to be off of methotrexate for 7-10 days,” Dr. Winthrop said. “This is for the booster, but it raises the question: If you go out to three, four, or five vaccinations, does this matter anymore? With the flu vaccine, most people are out to 10 or 15 boosters, and we haven’t seen any significant increase in disease flares.”

The study received funding from Medac, Gilead/Galapagos, and Friends and Sponsors of Berlin Charity. Dr. Burmester reported no relevant disclosures. Dr. Winthrop is a research consultant to Pfizer.

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

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People taking methotrexate for immunomodulatory diseases can skip one or two scheduled doses after they get an mRNA-based vaccine booster for COVID-19 and achieve a level of immunity against Omicron variants that’s comparable to people who aren’t immunosuppressed, a small observational cohort study from Germany reported.

Kmatta/Moment/Getty Images

“In general, the data suggest that pausing methotrexate is feasible, and it’s sufficient if the last dose occurs 1-3 days before the vaccination,” study coauthor Gerd Burmester, MD, a senior professor of rheumatology and immunology at the University of Medicine Berlin, told this news organization. “In pragmatic terms: pausing the methotrexate injection just twice after the vaccine is finished and, interestingly, not prior to the vaccination.”

Dr. Gerd Burmester


The study, published online in RMD Open, included a statistical analysis that determined that a 10-day pause after the vaccination would be optimal, Dr. Burmester said.

Dr. Burmester and coauthors claimed this is the first study to evaluate the antibody response in patients on methotrexate against Omicron variants – in this study, variants BA.1 and BA.2 – after getting a COVID-19 mRNA booster. The study compared neutralizing serum activity of 50 patients taking methotrexate – 24 of whom continued treatments uninterrupted and 26 of whom paused treatments after getting a second booster – with 25 nonimmunosuppressed patients who served as controls. A total of 24% of the patients taking methotrexate received the mRNA-1273 vaccine while the entire control group received the Pfizer/BioNTech BNT162b2 vaccine.

The researchers used SARS-CoV-2 pseudovirus neutralization assays to evaluate post-vaccination antibody levels.

The U.S. Centers for Disease Control and Prevention and other government health agencies have recommended that immunocompromised patients get a fourth COVID-19 vaccination. But these vaccines can be problematic in patients taking methotrexate, which was linked to a reduced response after the second and third doses of the COVID-19 vaccine.

Previous studies reported that pausing methotrexate for 10 or 14 days after the first two vaccinations improved the production of neutralizing antibodies. A 2022 study found that a 2-week pause after a booster increased antibody response against S1 RBD (receptor binding domain) of the SARS-CoV-2 spike protein about twofold. Another recently published study of mRNA vaccines found that taking methotrexate with either a biologic or targeted synthetic disease-modifying antirheumatic drug reduces the efficacy of a third (booster) shot of SARS-CoV-2 mRNA vaccine in older adults but not younger patients with RA.

“Our study and also the other studies suggested that you can pause methotrexate treatment safely from a point of view of disease activity of rheumatoid arthritis,” Dr. Burmester said. “If you do the pause just twice or once only, it doesn’t lead to significant flares.”
 

Study results

The study found that serum neutralizing activity against the Omicron BA.1 variant, measured as geometric mean 50% inhibitory serum dilution (ID50s), wasn’t significantly different between the methotrexate and the nonimmunosuppressed groups before getting their mRNA booster (P = .657). However, 4 weeks after getting the booster, the nonimmunosuppressed group had a 68-fold increase in antibody activity versus a 20-fold increase in the methotrexate patients. After 12 weeks, ID50s in both groups decreased by about half (P = .001).

 

 

The methotrexate patients who continued therapy after the booster had significantly lower neutralization against Omicron BA.1 at both 4 weeks and 12 weeks than did their counterparts who paused therapy, as well as control patients.

The results were very similar in the same group comparisons of the serum neutralizing activity against the Omicron BA.2 variant at 4 and 12 weeks after booster vaccination.
 

Expert commentary

This study is noteworthy because it used SARS-CoV-2 pseudovirus neutralization assays to evaluate antibody levels, Kevin Winthrop, MD, MPH, professor of infectious disease and public health at Oregon Health & Science University, Portland, who was not involved in the study, said. “A lot of studies don’t look at neutralizing antibody titers, and that’s really what we care about,” Dr. Winthrop said. “What we want are functional antibodies that are doing something, and the only way to do that is to test them.”

Dr. Kevin Winthrop

The study is “confirmatory” of other studies that call for pausing methotrexate after vaccination, Dr. Winthrop said, including a study he coauthored, and which the German researchers cited, that found pausing methotrexate for a week or so after the influenza vaccination in RA patients improved vaccine immunogenicity. He added that the findings with the early Omicron variants are important because the newest boosters target the later Omicron variants, BA.4 and BA.5.

“The bottom line is that when someone comes in for a COVID-19 vaccination, tell them to be off of methotrexate for 7-10 days,” Dr. Winthrop said. “This is for the booster, but it raises the question: If you go out to three, four, or five vaccinations, does this matter anymore? With the flu vaccine, most people are out to 10 or 15 boosters, and we haven’t seen any significant increase in disease flares.”

The study received funding from Medac, Gilead/Galapagos, and Friends and Sponsors of Berlin Charity. Dr. Burmester reported no relevant disclosures. Dr. Winthrop is a research consultant to Pfizer.

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

People taking methotrexate for immunomodulatory diseases can skip one or two scheduled doses after they get an mRNA-based vaccine booster for COVID-19 and achieve a level of immunity against Omicron variants that’s comparable to people who aren’t immunosuppressed, a small observational cohort study from Germany reported.

Kmatta/Moment/Getty Images

“In general, the data suggest that pausing methotrexate is feasible, and it’s sufficient if the last dose occurs 1-3 days before the vaccination,” study coauthor Gerd Burmester, MD, a senior professor of rheumatology and immunology at the University of Medicine Berlin, told this news organization. “In pragmatic terms: pausing the methotrexate injection just twice after the vaccine is finished and, interestingly, not prior to the vaccination.”

Dr. Gerd Burmester


The study, published online in RMD Open, included a statistical analysis that determined that a 10-day pause after the vaccination would be optimal, Dr. Burmester said.

Dr. Burmester and coauthors claimed this is the first study to evaluate the antibody response in patients on methotrexate against Omicron variants – in this study, variants BA.1 and BA.2 – after getting a COVID-19 mRNA booster. The study compared neutralizing serum activity of 50 patients taking methotrexate – 24 of whom continued treatments uninterrupted and 26 of whom paused treatments after getting a second booster – with 25 nonimmunosuppressed patients who served as controls. A total of 24% of the patients taking methotrexate received the mRNA-1273 vaccine while the entire control group received the Pfizer/BioNTech BNT162b2 vaccine.

The researchers used SARS-CoV-2 pseudovirus neutralization assays to evaluate post-vaccination antibody levels.

The U.S. Centers for Disease Control and Prevention and other government health agencies have recommended that immunocompromised patients get a fourth COVID-19 vaccination. But these vaccines can be problematic in patients taking methotrexate, which was linked to a reduced response after the second and third doses of the COVID-19 vaccine.

Previous studies reported that pausing methotrexate for 10 or 14 days after the first two vaccinations improved the production of neutralizing antibodies. A 2022 study found that a 2-week pause after a booster increased antibody response against S1 RBD (receptor binding domain) of the SARS-CoV-2 spike protein about twofold. Another recently published study of mRNA vaccines found that taking methotrexate with either a biologic or targeted synthetic disease-modifying antirheumatic drug reduces the efficacy of a third (booster) shot of SARS-CoV-2 mRNA vaccine in older adults but not younger patients with RA.

“Our study and also the other studies suggested that you can pause methotrexate treatment safely from a point of view of disease activity of rheumatoid arthritis,” Dr. Burmester said. “If you do the pause just twice or once only, it doesn’t lead to significant flares.”
 

Study results

The study found that serum neutralizing activity against the Omicron BA.1 variant, measured as geometric mean 50% inhibitory serum dilution (ID50s), wasn’t significantly different between the methotrexate and the nonimmunosuppressed groups before getting their mRNA booster (P = .657). However, 4 weeks after getting the booster, the nonimmunosuppressed group had a 68-fold increase in antibody activity versus a 20-fold increase in the methotrexate patients. After 12 weeks, ID50s in both groups decreased by about half (P = .001).

 

 

The methotrexate patients who continued therapy after the booster had significantly lower neutralization against Omicron BA.1 at both 4 weeks and 12 weeks than did their counterparts who paused therapy, as well as control patients.

The results were very similar in the same group comparisons of the serum neutralizing activity against the Omicron BA.2 variant at 4 and 12 weeks after booster vaccination.
 

Expert commentary

This study is noteworthy because it used SARS-CoV-2 pseudovirus neutralization assays to evaluate antibody levels, Kevin Winthrop, MD, MPH, professor of infectious disease and public health at Oregon Health & Science University, Portland, who was not involved in the study, said. “A lot of studies don’t look at neutralizing antibody titers, and that’s really what we care about,” Dr. Winthrop said. “What we want are functional antibodies that are doing something, and the only way to do that is to test them.”

Dr. Kevin Winthrop

The study is “confirmatory” of other studies that call for pausing methotrexate after vaccination, Dr. Winthrop said, including a study he coauthored, and which the German researchers cited, that found pausing methotrexate for a week or so after the influenza vaccination in RA patients improved vaccine immunogenicity. He added that the findings with the early Omicron variants are important because the newest boosters target the later Omicron variants, BA.4 and BA.5.

“The bottom line is that when someone comes in for a COVID-19 vaccination, tell them to be off of methotrexate for 7-10 days,” Dr. Winthrop said. “This is for the booster, but it raises the question: If you go out to three, four, or five vaccinations, does this matter anymore? With the flu vaccine, most people are out to 10 or 15 boosters, and we haven’t seen any significant increase in disease flares.”

The study received funding from Medac, Gilead/Galapagos, and Friends and Sponsors of Berlin Charity. Dr. Burmester reported no relevant disclosures. Dr. Winthrop is a research consultant to Pfizer.

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

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Rules for performing research with children

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Changed
Thu, 10/20/2022 - 15:40

 

The road to hell is paved with good intentions – especially true in clinical research. A Food and Drug Administration press release notes, “Historically, children were not included in clinical trials because of a misperception that excluding them from research was in fact protecting them. This resulted in many FDA-approved, licensed, cleared, or authorized drugs, biological products, and medical devices lacking pediatric-specific labeling information.” In an effort to improve on this situation, the FDA published in September 2022 a proposed new draft guidance on performing research with children that is open for public comment for 3 months.

Dr. Kevin T. Powell


There is a long history of government attempts to promote research and development for the benefit of society. Sometimes government succeeds and sometimes not. For instance, when the U.S. federal government funded scientific research in the 1960s, it sought to increase the common good by promulgating those discoveries. The government insisted that all federally funded research be in the public domain. The funding produced a spectacular number of technological advancements that have enriched society. However, a decade later, the government concluded that too many good research ideas were never developed into beneficial products because without the ability to patent the results, the costs and risks of product development were not profitable for industry. By the late 1970s, new laws were enacted to enable universities and their faculty to patent the results of government-funded research and share in any wealth created.

Pharmaceutical research in the 1970s and 1980s was mostly performed on men in order to reduce the risk of giving treatments of unknown safety to pregnant women. The unintended consequence was that the new drugs frequently were less effective for women. This was particularly true for cardiac medications for which lifestyle risk factors differed between the sexes.

Similarly, children were often excluded from research because of the unknown risks of new drugs on growing bodies and brains. Children were also seen as a vulnerable population for whom informed consent was problematic. The result of these well-intentioned restrictions was the creation of new products that did not have pediatric dosing recommendations, pediatric safety assessments, or approval for pediatric indications. To remediate these deficiencies, in 1997 and 2007 the FDA offered a 6-month extension on patent protection as motivation for companies to develop those pediatric recommendations. Alas, those laws were primarily used to extend the profitability of blockbuster products rather than truly benefit children.

Over the past 4 decades, pediatric ethicists proposed and refined rules to govern research on children. The Common Rule used by institutional review boards (IRBs) to protect human research subjects was expanded with guidelines covering children. The new draft guidance is the latest iteration of this effort. Nothing in the 14 pages of draft regulation appears revolutionary to me. The ideas are tweaks, based on theory and experience, of principles agreed upon 30 years ago. Finding the optimal social moral contract involves some empirical assessment of praxis and effectiveness.

I am loathe to summarize this new document, which itself is a summary of a vast body of literature, that supports the Code of Federal Regulations Title 21 Part 50 and 45 CFR Part 46. The draft document is well organized and I recommend it as an excellent primer for the area of pediatric research ethics if the subject is new to you. I also recommend it as required reading for anyone serving on an IRB.

IRBs usually review and approve any research on people. Generally, the selection of people for research should be done equitably. However, children should not be enrolled unless it is necessary to answer an important question relevant to children. For the past 2 decades, there has been an emphasis on obtaining the assent of the child as well as informed consent by the parents.

An important determination is whether the research is likely to help that particular child or whether it is aimed at advancing general knowledge. If there is no prospect of direct benefit, research is still permissible but more restricted for safety and comfort reasons. Next is determining whether the research carries only minimal risk or a minor increase over minimal risk. The draft defines and provides anchor examples of these situations. For instance, oral placebos and single blood draws are typically minimal risk. Multiple injections and blood draws over a year fall into the second category. One MRI is minimal risk but a minor increase in risk if it involves sedation or contrast.

 

 


I strongly support the ideals expressed in these guidelines. They represent the best blend of intentions and practical experience. They will become the law of the land. In ethics, there is merit in striving to do things properly, orderly, and enforceably.

The cynic in me sees two weaknesses in the stated approach. First, the volume of harm to children occurring during organized clinical research is extremely small. The greater harms come from off-label use, nonsystematic research, and the ignorance resulting from a lack of research. Second, my observation in all endeavors of morality is, “Raise the bar high enough and people walk under it.”

Dr. Powell is a retired pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected].

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The road to hell is paved with good intentions – especially true in clinical research. A Food and Drug Administration press release notes, “Historically, children were not included in clinical trials because of a misperception that excluding them from research was in fact protecting them. This resulted in many FDA-approved, licensed, cleared, or authorized drugs, biological products, and medical devices lacking pediatric-specific labeling information.” In an effort to improve on this situation, the FDA published in September 2022 a proposed new draft guidance on performing research with children that is open for public comment for 3 months.

Dr. Kevin T. Powell


There is a long history of government attempts to promote research and development for the benefit of society. Sometimes government succeeds and sometimes not. For instance, when the U.S. federal government funded scientific research in the 1960s, it sought to increase the common good by promulgating those discoveries. The government insisted that all federally funded research be in the public domain. The funding produced a spectacular number of technological advancements that have enriched society. However, a decade later, the government concluded that too many good research ideas were never developed into beneficial products because without the ability to patent the results, the costs and risks of product development were not profitable for industry. By the late 1970s, new laws were enacted to enable universities and their faculty to patent the results of government-funded research and share in any wealth created.

Pharmaceutical research in the 1970s and 1980s was mostly performed on men in order to reduce the risk of giving treatments of unknown safety to pregnant women. The unintended consequence was that the new drugs frequently were less effective for women. This was particularly true for cardiac medications for which lifestyle risk factors differed between the sexes.

Similarly, children were often excluded from research because of the unknown risks of new drugs on growing bodies and brains. Children were also seen as a vulnerable population for whom informed consent was problematic. The result of these well-intentioned restrictions was the creation of new products that did not have pediatric dosing recommendations, pediatric safety assessments, or approval for pediatric indications. To remediate these deficiencies, in 1997 and 2007 the FDA offered a 6-month extension on patent protection as motivation for companies to develop those pediatric recommendations. Alas, those laws were primarily used to extend the profitability of blockbuster products rather than truly benefit children.

Over the past 4 decades, pediatric ethicists proposed and refined rules to govern research on children. The Common Rule used by institutional review boards (IRBs) to protect human research subjects was expanded with guidelines covering children. The new draft guidance is the latest iteration of this effort. Nothing in the 14 pages of draft regulation appears revolutionary to me. The ideas are tweaks, based on theory and experience, of principles agreed upon 30 years ago. Finding the optimal social moral contract involves some empirical assessment of praxis and effectiveness.

I am loathe to summarize this new document, which itself is a summary of a vast body of literature, that supports the Code of Federal Regulations Title 21 Part 50 and 45 CFR Part 46. The draft document is well organized and I recommend it as an excellent primer for the area of pediatric research ethics if the subject is new to you. I also recommend it as required reading for anyone serving on an IRB.

IRBs usually review and approve any research on people. Generally, the selection of people for research should be done equitably. However, children should not be enrolled unless it is necessary to answer an important question relevant to children. For the past 2 decades, there has been an emphasis on obtaining the assent of the child as well as informed consent by the parents.

An important determination is whether the research is likely to help that particular child or whether it is aimed at advancing general knowledge. If there is no prospect of direct benefit, research is still permissible but more restricted for safety and comfort reasons. Next is determining whether the research carries only minimal risk or a minor increase over minimal risk. The draft defines and provides anchor examples of these situations. For instance, oral placebos and single blood draws are typically minimal risk. Multiple injections and blood draws over a year fall into the second category. One MRI is minimal risk but a minor increase in risk if it involves sedation or contrast.

 

 


I strongly support the ideals expressed in these guidelines. They represent the best blend of intentions and practical experience. They will become the law of the land. In ethics, there is merit in striving to do things properly, orderly, and enforceably.

The cynic in me sees two weaknesses in the stated approach. First, the volume of harm to children occurring during organized clinical research is extremely small. The greater harms come from off-label use, nonsystematic research, and the ignorance resulting from a lack of research. Second, my observation in all endeavors of morality is, “Raise the bar high enough and people walk under it.”

Dr. Powell is a retired pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected].

 

The road to hell is paved with good intentions – especially true in clinical research. A Food and Drug Administration press release notes, “Historically, children were not included in clinical trials because of a misperception that excluding them from research was in fact protecting them. This resulted in many FDA-approved, licensed, cleared, or authorized drugs, biological products, and medical devices lacking pediatric-specific labeling information.” In an effort to improve on this situation, the FDA published in September 2022 a proposed new draft guidance on performing research with children that is open for public comment for 3 months.

Dr. Kevin T. Powell


There is a long history of government attempts to promote research and development for the benefit of society. Sometimes government succeeds and sometimes not. For instance, when the U.S. federal government funded scientific research in the 1960s, it sought to increase the common good by promulgating those discoveries. The government insisted that all federally funded research be in the public domain. The funding produced a spectacular number of technological advancements that have enriched society. However, a decade later, the government concluded that too many good research ideas were never developed into beneficial products because without the ability to patent the results, the costs and risks of product development were not profitable for industry. By the late 1970s, new laws were enacted to enable universities and their faculty to patent the results of government-funded research and share in any wealth created.

Pharmaceutical research in the 1970s and 1980s was mostly performed on men in order to reduce the risk of giving treatments of unknown safety to pregnant women. The unintended consequence was that the new drugs frequently were less effective for women. This was particularly true for cardiac medications for which lifestyle risk factors differed between the sexes.

Similarly, children were often excluded from research because of the unknown risks of new drugs on growing bodies and brains. Children were also seen as a vulnerable population for whom informed consent was problematic. The result of these well-intentioned restrictions was the creation of new products that did not have pediatric dosing recommendations, pediatric safety assessments, or approval for pediatric indications. To remediate these deficiencies, in 1997 and 2007 the FDA offered a 6-month extension on patent protection as motivation for companies to develop those pediatric recommendations. Alas, those laws were primarily used to extend the profitability of blockbuster products rather than truly benefit children.

Over the past 4 decades, pediatric ethicists proposed and refined rules to govern research on children. The Common Rule used by institutional review boards (IRBs) to protect human research subjects was expanded with guidelines covering children. The new draft guidance is the latest iteration of this effort. Nothing in the 14 pages of draft regulation appears revolutionary to me. The ideas are tweaks, based on theory and experience, of principles agreed upon 30 years ago. Finding the optimal social moral contract involves some empirical assessment of praxis and effectiveness.

I am loathe to summarize this new document, which itself is a summary of a vast body of literature, that supports the Code of Federal Regulations Title 21 Part 50 and 45 CFR Part 46. The draft document is well organized and I recommend it as an excellent primer for the area of pediatric research ethics if the subject is new to you. I also recommend it as required reading for anyone serving on an IRB.

IRBs usually review and approve any research on people. Generally, the selection of people for research should be done equitably. However, children should not be enrolled unless it is necessary to answer an important question relevant to children. For the past 2 decades, there has been an emphasis on obtaining the assent of the child as well as informed consent by the parents.

An important determination is whether the research is likely to help that particular child or whether it is aimed at advancing general knowledge. If there is no prospect of direct benefit, research is still permissible but more restricted for safety and comfort reasons. Next is determining whether the research carries only minimal risk or a minor increase over minimal risk. The draft defines and provides anchor examples of these situations. For instance, oral placebos and single blood draws are typically minimal risk. Multiple injections and blood draws over a year fall into the second category. One MRI is minimal risk but a minor increase in risk if it involves sedation or contrast.

 

 


I strongly support the ideals expressed in these guidelines. They represent the best blend of intentions and practical experience. They will become the law of the land. In ethics, there is merit in striving to do things properly, orderly, and enforceably.

The cynic in me sees two weaknesses in the stated approach. First, the volume of harm to children occurring during organized clinical research is extremely small. The greater harms come from off-label use, nonsystematic research, and the ignorance resulting from a lack of research. Second, my observation in all endeavors of morality is, “Raise the bar high enough and people walk under it.”

Dr. Powell is a retired pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected].

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Why the 5-day isolation period for COVID makes no sense

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Changed
Thu, 10/20/2022 - 15:02

 

Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr. F. Perry Wilson of the Yale School of Medicine.

One of the more baffling decisions the CDC made during this pandemic was when they reduced the duration of isolation after a positive COVID test from 10 days to 5 days and did not require a negative antigen test to end isolation.



Multiple studies had suggested, after all, that positive antigen tests, while not perfect, were a decent proxy for infectivity. And if the purpose of isolation is to keep other community members safe, why not use a readily available test to know when it might be safe to go out in public again?

Also, 5 days just wasn’t that much time. Many individuals are symptomatic long after that point. Many people test positive long after that point. What exactly is the point of the 5-day isolation period?

We got some hard numbers this week to show just how good (or bad) an arbitrary-seeming 5-day isolation period is, thanks to this study from JAMA Network Open, which gives us a low-end estimate for the proportion of people who remain positive on antigen tests, which is to say infectious, after an isolation period.

This study estimates the low end of postisolation infectivity because of the study population: student athletes at an NCAA Division I school, which may or may not be Stanford. These athletes tested positive for COVID after having at least one dose of vaccine from January to May 2022. School protocol was to put the students in isolation for 7 days, at which time they could “test out” with a negative antigen test.

Put simply, these were healthy people. They were young. They were athletes. They were vaccinated. If anyone is going to have a brief, easy COVID course, it would be them. And they are doing at least a week of isolation, not 5 days.



So – isolation for 7 days. Antigen testing on day 7. How many still tested positive? Of 248 individuals tested, 67 (27%) tested positive. One in four.

More than half of those positive on day 7 tested positive on day 8, and more than half of those tested positive again on day 9. By day 10, they were released from isolation without further testing.

So, right there we have confirmation that 5 days of isolation without a negative test means you’re releasing a decent percentage of infectious individuals back into the population.

There were some predictors of prolonged positivity.



Symptomatic athletes were much more likely to test positive than asymptomatic athletes.

And the particular variant seemed to matter as well. In this time period, BA.1 and BA.2 were dominant, and it was pretty clear that BA.2 persisted longer than BA.1.

This brings me back to my original question: What is the point of the 5-day isolation period? On the basis of this study, you could imagine a guideline based on symptoms: Stay home until you feel better. You could imagine a guideline based on testing: Stay home until you test negative. A guideline based on time alone just doesn’t comport with the data. The benefit of policies based on symptoms or testing are obvious; some people would be out of isolation even before 5 days. But the downside, of course, is that some people would be stuck in isolation for much longer.

Maybe we should just say it. At this point, you could even imagine there being no recommendation at all – no isolation period. Like, you just stay home if you feel like you should stay home. I’m not entirely sure that such a policy would necessarily result in a greater number of infectious people out in the community.

In any case, as the arbitrariness of this particular 5-day isolation policy becomes more clear, the policy itself may be living on borrowed time.
 

 

 

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and on Medscape. He tweets @fperrywilson and hosts a repository of his communication work at www.methodsman.com. He disclosed no relevant financial relationships.



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

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Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr. F. Perry Wilson of the Yale School of Medicine.

One of the more baffling decisions the CDC made during this pandemic was when they reduced the duration of isolation after a positive COVID test from 10 days to 5 days and did not require a negative antigen test to end isolation.



Multiple studies had suggested, after all, that positive antigen tests, while not perfect, were a decent proxy for infectivity. And if the purpose of isolation is to keep other community members safe, why not use a readily available test to know when it might be safe to go out in public again?

Also, 5 days just wasn’t that much time. Many individuals are symptomatic long after that point. Many people test positive long after that point. What exactly is the point of the 5-day isolation period?

We got some hard numbers this week to show just how good (or bad) an arbitrary-seeming 5-day isolation period is, thanks to this study from JAMA Network Open, which gives us a low-end estimate for the proportion of people who remain positive on antigen tests, which is to say infectious, after an isolation period.

This study estimates the low end of postisolation infectivity because of the study population: student athletes at an NCAA Division I school, which may or may not be Stanford. These athletes tested positive for COVID after having at least one dose of vaccine from January to May 2022. School protocol was to put the students in isolation for 7 days, at which time they could “test out” with a negative antigen test.

Put simply, these were healthy people. They were young. They were athletes. They were vaccinated. If anyone is going to have a brief, easy COVID course, it would be them. And they are doing at least a week of isolation, not 5 days.



So – isolation for 7 days. Antigen testing on day 7. How many still tested positive? Of 248 individuals tested, 67 (27%) tested positive. One in four.

More than half of those positive on day 7 tested positive on day 8, and more than half of those tested positive again on day 9. By day 10, they were released from isolation without further testing.

So, right there we have confirmation that 5 days of isolation without a negative test means you’re releasing a decent percentage of infectious individuals back into the population.

There were some predictors of prolonged positivity.



Symptomatic athletes were much more likely to test positive than asymptomatic athletes.

And the particular variant seemed to matter as well. In this time period, BA.1 and BA.2 were dominant, and it was pretty clear that BA.2 persisted longer than BA.1.

This brings me back to my original question: What is the point of the 5-day isolation period? On the basis of this study, you could imagine a guideline based on symptoms: Stay home until you feel better. You could imagine a guideline based on testing: Stay home until you test negative. A guideline based on time alone just doesn’t comport with the data. The benefit of policies based on symptoms or testing are obvious; some people would be out of isolation even before 5 days. But the downside, of course, is that some people would be stuck in isolation for much longer.

Maybe we should just say it. At this point, you could even imagine there being no recommendation at all – no isolation period. Like, you just stay home if you feel like you should stay home. I’m not entirely sure that such a policy would necessarily result in a greater number of infectious people out in the community.

In any case, as the arbitrariness of this particular 5-day isolation policy becomes more clear, the policy itself may be living on borrowed time.
 

 

 

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and on Medscape. He tweets @fperrywilson and hosts a repository of his communication work at www.methodsman.com. He disclosed no relevant financial relationships.



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

 

Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr. F. Perry Wilson of the Yale School of Medicine.

One of the more baffling decisions the CDC made during this pandemic was when they reduced the duration of isolation after a positive COVID test from 10 days to 5 days and did not require a negative antigen test to end isolation.



Multiple studies had suggested, after all, that positive antigen tests, while not perfect, were a decent proxy for infectivity. And if the purpose of isolation is to keep other community members safe, why not use a readily available test to know when it might be safe to go out in public again?

Also, 5 days just wasn’t that much time. Many individuals are symptomatic long after that point. Many people test positive long after that point. What exactly is the point of the 5-day isolation period?

We got some hard numbers this week to show just how good (or bad) an arbitrary-seeming 5-day isolation period is, thanks to this study from JAMA Network Open, which gives us a low-end estimate for the proportion of people who remain positive on antigen tests, which is to say infectious, after an isolation period.

This study estimates the low end of postisolation infectivity because of the study population: student athletes at an NCAA Division I school, which may or may not be Stanford. These athletes tested positive for COVID after having at least one dose of vaccine from January to May 2022. School protocol was to put the students in isolation for 7 days, at which time they could “test out” with a negative antigen test.

Put simply, these were healthy people. They were young. They were athletes. They were vaccinated. If anyone is going to have a brief, easy COVID course, it would be them. And they are doing at least a week of isolation, not 5 days.



So – isolation for 7 days. Antigen testing on day 7. How many still tested positive? Of 248 individuals tested, 67 (27%) tested positive. One in four.

More than half of those positive on day 7 tested positive on day 8, and more than half of those tested positive again on day 9. By day 10, they were released from isolation without further testing.

So, right there we have confirmation that 5 days of isolation without a negative test means you’re releasing a decent percentage of infectious individuals back into the population.

There were some predictors of prolonged positivity.



Symptomatic athletes were much more likely to test positive than asymptomatic athletes.

And the particular variant seemed to matter as well. In this time period, BA.1 and BA.2 were dominant, and it was pretty clear that BA.2 persisted longer than BA.1.

This brings me back to my original question: What is the point of the 5-day isolation period? On the basis of this study, you could imagine a guideline based on symptoms: Stay home until you feel better. You could imagine a guideline based on testing: Stay home until you test negative. A guideline based on time alone just doesn’t comport with the data. The benefit of policies based on symptoms or testing are obvious; some people would be out of isolation even before 5 days. But the downside, of course, is that some people would be stuck in isolation for much longer.

Maybe we should just say it. At this point, you could even imagine there being no recommendation at all – no isolation period. Like, you just stay home if you feel like you should stay home. I’m not entirely sure that such a policy would necessarily result in a greater number of infectious people out in the community.

In any case, as the arbitrariness of this particular 5-day isolation policy becomes more clear, the policy itself may be living on borrowed time.
 

 

 

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and on Medscape. He tweets @fperrywilson and hosts a repository of his communication work at www.methodsman.com. He disclosed no relevant financial relationships.



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

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NICU signs hint at cerebral palsy risk

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– Cerebral palsy affects about 3 in every 1,000 children, but there is usually little sign of the condition at birth. Instead, it usually shows clinical manifestation between ages 2 and 5, and a diagnosis can trigger early interventions that can improve long-term outcomes.

Physicians and patients would benefit from a screening method for cerebral palsy at birth, but that has so far eluded researchers.

At the 2022 annual meeting of the Child Neurology Society, researchers presented evidence that respiratory rate measured in the last 24 hours of residence in the neonate intensive care unit (NICU) predicts later onset of cerebral palsy, with higher variability associated with increased cerebral palsy risk.

The study results were promising, according to Marc Patterson, MD, who comoderated the session. “It gives us more confidence in predicting the children at risk and making sure that they’re going to be followed closely to get the interventions they need to help them,” said Dr. Patterson, who is a professor of neurology, pediatrics, and medical genetics at Mayo Medical School in Rochester, Minn.

“By the time a child is 5 or 6, the symptoms are usually very obvious, but you really want to intervene as soon as possible before their brain’s plasticity decreases over time, so the earlier you can intervene in general, the better your results are going to be,” said Dr. Patterson.

There are tools available to diagnose cerebral palsy at an earlier age, including the Prechtl General Movements Assessment (GMA), which can be done up to 5 months of corrected age. It has 97% sensitivity and 89% specificity for cerebral palsy. The Hammersmith Infant Neurological Examination (HINE), which can be used in the same age range, and has 72-91% sensitivity and 100% specificity.

Both of the available tools are resource intensive and require trained clinicians, and may be unavailable in many areas. Despite these tools, early diagnosis of cerebral palsy is still underemployed, according to Arohi Saxena, a third-year medical student at Washington University in St. Louis, who presented the study results.
 

Respiratory rate variability may indicate increased risk

The researchers set out to identify objective metrics that correlated with HINE and GMA scores. They looked at kinematic data from practical assessments carried out by their physical therapists, as well as vital sign instability obtained at NICU discharge, which was based on suggestions that hemodynamic instability may be linked to later risk of cerebral palsy, according to Ms. Saxena.

They analyzed data from 31 infants with a corrected age of 8-25 weeks at a tertiary NICU follow-up clinic. Of these, 18 displayed fidgety movements on their Prechtl assessment, and 13 did not.

They used DeepLabCut software to analyze data from videos of the Prechtl assessment, with a focus on range and variance of hand and foot movements normalized to nose-to-umbilicus distance. They also analyzed pulse and respiratory data from the final 24 hours before NICU discharge.

They found that infants without fidgety movements had decreased hand and foot movement ranges (P = .04). There was no significant difference between the two groups with respect to pulse measurements. However, the respiratory rate range and variance was significantly higher in infants without fidgety movements. “Infants who are at higher risk for developing cerebral palsy had more respiratory instability early on in life,” said Ms. Saxena during her talk.

When they compared values to HINE scores, they found a correlation with less foot movement and a predisposition to develop cerebral palsy, but no correlation with hand movement. A lower HINE sore also correlated to larger respiratory rate range and variance (P < .01 for both).

“Our hypothesis to explain this link is that respiratory rate variability is likely driven by neonatal injury in the brainstem, where the respiratory centers are located. In some infants, this may correlate with more extensive cerebral injury that could predict the development of cerebral palsy,” said Ms. Saxena.

The group plans to increase its sample size as well as to conduct long-term follow-up on the infants to see how many receive formal diagnoses of cerebral palsy.

After her talk, asked by a moderator why motor assessments were not a reliable predictor in their study, Ms. Saxena pointed to the inexperience of assessors at the institution, where Prechtl testing had only recently begun.

“I think a lot of it is to do with the more subjective nature of the motor assessment. We definitely saw kind of a trend where in the earlier data that was collected, right when our institutions started doing these Prechtls, it was even less of a reliable effect. So I think possibly as clinicians continue to get more familiar with this assessment and there’s more like a validated and robust scoring system, maybe we’ll see a stronger correlation,” she said.

Ms. Saxena had no relevant disclosures. Coauthor Boomah Aravamuthan, MD, DPhil, is a consultant for Neurocrine Biosciences and has received royalties from UpToDate and funding from the National Institute of Neurological Disorders and Stroke.

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– Cerebral palsy affects about 3 in every 1,000 children, but there is usually little sign of the condition at birth. Instead, it usually shows clinical manifestation between ages 2 and 5, and a diagnosis can trigger early interventions that can improve long-term outcomes.

Physicians and patients would benefit from a screening method for cerebral palsy at birth, but that has so far eluded researchers.

At the 2022 annual meeting of the Child Neurology Society, researchers presented evidence that respiratory rate measured in the last 24 hours of residence in the neonate intensive care unit (NICU) predicts later onset of cerebral palsy, with higher variability associated with increased cerebral palsy risk.

The study results were promising, according to Marc Patterson, MD, who comoderated the session. “It gives us more confidence in predicting the children at risk and making sure that they’re going to be followed closely to get the interventions they need to help them,” said Dr. Patterson, who is a professor of neurology, pediatrics, and medical genetics at Mayo Medical School in Rochester, Minn.

“By the time a child is 5 or 6, the symptoms are usually very obvious, but you really want to intervene as soon as possible before their brain’s plasticity decreases over time, so the earlier you can intervene in general, the better your results are going to be,” said Dr. Patterson.

There are tools available to diagnose cerebral palsy at an earlier age, including the Prechtl General Movements Assessment (GMA), which can be done up to 5 months of corrected age. It has 97% sensitivity and 89% specificity for cerebral palsy. The Hammersmith Infant Neurological Examination (HINE), which can be used in the same age range, and has 72-91% sensitivity and 100% specificity.

Both of the available tools are resource intensive and require trained clinicians, and may be unavailable in many areas. Despite these tools, early diagnosis of cerebral palsy is still underemployed, according to Arohi Saxena, a third-year medical student at Washington University in St. Louis, who presented the study results.
 

Respiratory rate variability may indicate increased risk

The researchers set out to identify objective metrics that correlated with HINE and GMA scores. They looked at kinematic data from practical assessments carried out by their physical therapists, as well as vital sign instability obtained at NICU discharge, which was based on suggestions that hemodynamic instability may be linked to later risk of cerebral palsy, according to Ms. Saxena.

They analyzed data from 31 infants with a corrected age of 8-25 weeks at a tertiary NICU follow-up clinic. Of these, 18 displayed fidgety movements on their Prechtl assessment, and 13 did not.

They used DeepLabCut software to analyze data from videos of the Prechtl assessment, with a focus on range and variance of hand and foot movements normalized to nose-to-umbilicus distance. They also analyzed pulse and respiratory data from the final 24 hours before NICU discharge.

They found that infants without fidgety movements had decreased hand and foot movement ranges (P = .04). There was no significant difference between the two groups with respect to pulse measurements. However, the respiratory rate range and variance was significantly higher in infants without fidgety movements. “Infants who are at higher risk for developing cerebral palsy had more respiratory instability early on in life,” said Ms. Saxena during her talk.

When they compared values to HINE scores, they found a correlation with less foot movement and a predisposition to develop cerebral palsy, but no correlation with hand movement. A lower HINE sore also correlated to larger respiratory rate range and variance (P < .01 for both).

“Our hypothesis to explain this link is that respiratory rate variability is likely driven by neonatal injury in the brainstem, where the respiratory centers are located. In some infants, this may correlate with more extensive cerebral injury that could predict the development of cerebral palsy,” said Ms. Saxena.

The group plans to increase its sample size as well as to conduct long-term follow-up on the infants to see how many receive formal diagnoses of cerebral palsy.

After her talk, asked by a moderator why motor assessments were not a reliable predictor in their study, Ms. Saxena pointed to the inexperience of assessors at the institution, where Prechtl testing had only recently begun.

“I think a lot of it is to do with the more subjective nature of the motor assessment. We definitely saw kind of a trend where in the earlier data that was collected, right when our institutions started doing these Prechtls, it was even less of a reliable effect. So I think possibly as clinicians continue to get more familiar with this assessment and there’s more like a validated and robust scoring system, maybe we’ll see a stronger correlation,” she said.

Ms. Saxena had no relevant disclosures. Coauthor Boomah Aravamuthan, MD, DPhil, is a consultant for Neurocrine Biosciences and has received royalties from UpToDate and funding from the National Institute of Neurological Disorders and Stroke.

 

– Cerebral palsy affects about 3 in every 1,000 children, but there is usually little sign of the condition at birth. Instead, it usually shows clinical manifestation between ages 2 and 5, and a diagnosis can trigger early interventions that can improve long-term outcomes.

Physicians and patients would benefit from a screening method for cerebral palsy at birth, but that has so far eluded researchers.

At the 2022 annual meeting of the Child Neurology Society, researchers presented evidence that respiratory rate measured in the last 24 hours of residence in the neonate intensive care unit (NICU) predicts later onset of cerebral palsy, with higher variability associated with increased cerebral palsy risk.

The study results were promising, according to Marc Patterson, MD, who comoderated the session. “It gives us more confidence in predicting the children at risk and making sure that they’re going to be followed closely to get the interventions they need to help them,” said Dr. Patterson, who is a professor of neurology, pediatrics, and medical genetics at Mayo Medical School in Rochester, Minn.

“By the time a child is 5 or 6, the symptoms are usually very obvious, but you really want to intervene as soon as possible before their brain’s plasticity decreases over time, so the earlier you can intervene in general, the better your results are going to be,” said Dr. Patterson.

There are tools available to diagnose cerebral palsy at an earlier age, including the Prechtl General Movements Assessment (GMA), which can be done up to 5 months of corrected age. It has 97% sensitivity and 89% specificity for cerebral palsy. The Hammersmith Infant Neurological Examination (HINE), which can be used in the same age range, and has 72-91% sensitivity and 100% specificity.

Both of the available tools are resource intensive and require trained clinicians, and may be unavailable in many areas. Despite these tools, early diagnosis of cerebral palsy is still underemployed, according to Arohi Saxena, a third-year medical student at Washington University in St. Louis, who presented the study results.
 

Respiratory rate variability may indicate increased risk

The researchers set out to identify objective metrics that correlated with HINE and GMA scores. They looked at kinematic data from practical assessments carried out by their physical therapists, as well as vital sign instability obtained at NICU discharge, which was based on suggestions that hemodynamic instability may be linked to later risk of cerebral palsy, according to Ms. Saxena.

They analyzed data from 31 infants with a corrected age of 8-25 weeks at a tertiary NICU follow-up clinic. Of these, 18 displayed fidgety movements on their Prechtl assessment, and 13 did not.

They used DeepLabCut software to analyze data from videos of the Prechtl assessment, with a focus on range and variance of hand and foot movements normalized to nose-to-umbilicus distance. They also analyzed pulse and respiratory data from the final 24 hours before NICU discharge.

They found that infants without fidgety movements had decreased hand and foot movement ranges (P = .04). There was no significant difference between the two groups with respect to pulse measurements. However, the respiratory rate range and variance was significantly higher in infants without fidgety movements. “Infants who are at higher risk for developing cerebral palsy had more respiratory instability early on in life,” said Ms. Saxena during her talk.

When they compared values to HINE scores, they found a correlation with less foot movement and a predisposition to develop cerebral palsy, but no correlation with hand movement. A lower HINE sore also correlated to larger respiratory rate range and variance (P < .01 for both).

“Our hypothesis to explain this link is that respiratory rate variability is likely driven by neonatal injury in the brainstem, where the respiratory centers are located. In some infants, this may correlate with more extensive cerebral injury that could predict the development of cerebral palsy,” said Ms. Saxena.

The group plans to increase its sample size as well as to conduct long-term follow-up on the infants to see how many receive formal diagnoses of cerebral palsy.

After her talk, asked by a moderator why motor assessments were not a reliable predictor in their study, Ms. Saxena pointed to the inexperience of assessors at the institution, where Prechtl testing had only recently begun.

“I think a lot of it is to do with the more subjective nature of the motor assessment. We definitely saw kind of a trend where in the earlier data that was collected, right when our institutions started doing these Prechtls, it was even less of a reliable effect. So I think possibly as clinicians continue to get more familiar with this assessment and there’s more like a validated and robust scoring system, maybe we’ll see a stronger correlation,” she said.

Ms. Saxena had no relevant disclosures. Coauthor Boomah Aravamuthan, MD, DPhil, is a consultant for Neurocrine Biosciences and has received royalties from UpToDate and funding from the National Institute of Neurological Disorders and Stroke.

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Asthma ED visits predict failed housing inspections

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Visits to the emergency department for asthma increase more than a year before a failed inspection by the U.S. Department of Housing and Urban Development (HUD), according to a new study presented at the annual meeting of the American College of Emergency Physicians.

While links between asthma and low-quality housing prone to harboring allergens have been well-documented, the current study takes the extra step of looking at housing down to the level of individual land parcels and suggests that asthma hospital visits can be used to identify hazardous housing earlier.

“Emergency department visits for asthma provide a leading indicator that can be used by health departments or housing authorities to direct housing inspections and remediation of poor housing conditions, track improvements in housing quality, measure housing department performance, support resident grievances, and inform funding allocation decisions,” said the study’s lead researcher, Elizabeth Samuels, MD, who is assistant professor of epidemiology and emergency medicine at Brown University, Providence, R.I.

Researchers retrospectively looked at cases of children and adults in the Greater New Haven area of Connecticut seen at the Yale New Haven Hospital ED for asthma-related problems between March 2013 and August 2017. The region has the fifth-highest prevalence of asthma in the United States, the researchers point out, due to its air quality, pollens, and quality of its housing. More than half of residences were built before 1,940, compared with about 13% nationally. Patient addresses were matched with HUD inspection records.

The review encompassed 11,429 ED visits by 6,366 individuals; 54% were insured by Medicaid, and 42% were Black. Controlling for patient and neighborhood data, researchers found that increased asthma ED visits at the parcel level were associated with decreased HUD inspection scores to a highly significant degree (P < .001).

They also found that there was a relationship in terms of timing between asthma ED visits and inspection scores: asthma ED visits increased more than 1 year before a failed HUD inspection. They also found that asthma ED visits were not elevated at housing units that passed inspection. Using asthma ED visits to predict failed housing inspections produced a specificity rate of 92.3% in an adjusted model, Dr. Samuels noted.

“This approach represents a novel method of early identification of dangerous housing conditions, which could aid in the prevention of asthma-related morbidity and mortality,” Dr. Samuels said.

The investigators noted that, of the parcels with the top three incidence rates of asthma ED visits, “all of them have been closed or demolished.”

In addition to limiting exposure of patients with asthma to the allergens of mold, mice and rats, and cockroaches, improving poor-quality housing earlier could help asthma by reducing stress, she said.

“There is also an increasing evidence base that psychosocial stress increases the risk of asthma attacks, and it’s therefore possible that living in poor housing conditions – often highly stressful situations – drives exacerbation risk via this pathway,” she said. “Synergistic effects between these pathways are also possible or even likely.”

Neeta Thakur, MD, associate professor of medicine at the University of California, San Francisco, who researches asthma, said the findings could lead to a strategy for improving poor-quality housing more quickly. As it is, inspections are too infrequent, often prompted by resident complaints.

“Once the complaints get to a certain threshold, then there might be an inspection that happens, and if there is a periodic review of the buildings, they often happen few and far between,” she said. “We could actually use some of the information that we’re already getting from something like ED visits and see if there is a pattern.”

An important follow-up would be to see whether asthma outcomes improve after housing deficiencies are addressed and whether the predictive capacity of ED visits occurs in other places.

“Would you then see a decline in the ED visit rates from individuals living in those buildings?” Dr. Thakur said. “It’s important to find a leading indicator, but you want to be sure that that leading indicator is useful as something that can be intervened upon.”

Dr. Samuels and Dr. Thakur have reported no relevant financial relationships.

 

 

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

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Visits to the emergency department for asthma increase more than a year before a failed inspection by the U.S. Department of Housing and Urban Development (HUD), according to a new study presented at the annual meeting of the American College of Emergency Physicians.

While links between asthma and low-quality housing prone to harboring allergens have been well-documented, the current study takes the extra step of looking at housing down to the level of individual land parcels and suggests that asthma hospital visits can be used to identify hazardous housing earlier.

“Emergency department visits for asthma provide a leading indicator that can be used by health departments or housing authorities to direct housing inspections and remediation of poor housing conditions, track improvements in housing quality, measure housing department performance, support resident grievances, and inform funding allocation decisions,” said the study’s lead researcher, Elizabeth Samuels, MD, who is assistant professor of epidemiology and emergency medicine at Brown University, Providence, R.I.

Researchers retrospectively looked at cases of children and adults in the Greater New Haven area of Connecticut seen at the Yale New Haven Hospital ED for asthma-related problems between March 2013 and August 2017. The region has the fifth-highest prevalence of asthma in the United States, the researchers point out, due to its air quality, pollens, and quality of its housing. More than half of residences were built before 1,940, compared with about 13% nationally. Patient addresses were matched with HUD inspection records.

The review encompassed 11,429 ED visits by 6,366 individuals; 54% were insured by Medicaid, and 42% were Black. Controlling for patient and neighborhood data, researchers found that increased asthma ED visits at the parcel level were associated with decreased HUD inspection scores to a highly significant degree (P < .001).

They also found that there was a relationship in terms of timing between asthma ED visits and inspection scores: asthma ED visits increased more than 1 year before a failed HUD inspection. They also found that asthma ED visits were not elevated at housing units that passed inspection. Using asthma ED visits to predict failed housing inspections produced a specificity rate of 92.3% in an adjusted model, Dr. Samuels noted.

“This approach represents a novel method of early identification of dangerous housing conditions, which could aid in the prevention of asthma-related morbidity and mortality,” Dr. Samuels said.

The investigators noted that, of the parcels with the top three incidence rates of asthma ED visits, “all of them have been closed or demolished.”

In addition to limiting exposure of patients with asthma to the allergens of mold, mice and rats, and cockroaches, improving poor-quality housing earlier could help asthma by reducing stress, she said.

“There is also an increasing evidence base that psychosocial stress increases the risk of asthma attacks, and it’s therefore possible that living in poor housing conditions – often highly stressful situations – drives exacerbation risk via this pathway,” she said. “Synergistic effects between these pathways are also possible or even likely.”

Neeta Thakur, MD, associate professor of medicine at the University of California, San Francisco, who researches asthma, said the findings could lead to a strategy for improving poor-quality housing more quickly. As it is, inspections are too infrequent, often prompted by resident complaints.

“Once the complaints get to a certain threshold, then there might be an inspection that happens, and if there is a periodic review of the buildings, they often happen few and far between,” she said. “We could actually use some of the information that we’re already getting from something like ED visits and see if there is a pattern.”

An important follow-up would be to see whether asthma outcomes improve after housing deficiencies are addressed and whether the predictive capacity of ED visits occurs in other places.

“Would you then see a decline in the ED visit rates from individuals living in those buildings?” Dr. Thakur said. “It’s important to find a leading indicator, but you want to be sure that that leading indicator is useful as something that can be intervened upon.”

Dr. Samuels and Dr. Thakur have reported no relevant financial relationships.

 

 

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

Visits to the emergency department for asthma increase more than a year before a failed inspection by the U.S. Department of Housing and Urban Development (HUD), according to a new study presented at the annual meeting of the American College of Emergency Physicians.

While links between asthma and low-quality housing prone to harboring allergens have been well-documented, the current study takes the extra step of looking at housing down to the level of individual land parcels and suggests that asthma hospital visits can be used to identify hazardous housing earlier.

“Emergency department visits for asthma provide a leading indicator that can be used by health departments or housing authorities to direct housing inspections and remediation of poor housing conditions, track improvements in housing quality, measure housing department performance, support resident grievances, and inform funding allocation decisions,” said the study’s lead researcher, Elizabeth Samuels, MD, who is assistant professor of epidemiology and emergency medicine at Brown University, Providence, R.I.

Researchers retrospectively looked at cases of children and adults in the Greater New Haven area of Connecticut seen at the Yale New Haven Hospital ED for asthma-related problems between March 2013 and August 2017. The region has the fifth-highest prevalence of asthma in the United States, the researchers point out, due to its air quality, pollens, and quality of its housing. More than half of residences were built before 1,940, compared with about 13% nationally. Patient addresses were matched with HUD inspection records.

The review encompassed 11,429 ED visits by 6,366 individuals; 54% were insured by Medicaid, and 42% were Black. Controlling for patient and neighborhood data, researchers found that increased asthma ED visits at the parcel level were associated with decreased HUD inspection scores to a highly significant degree (P < .001).

They also found that there was a relationship in terms of timing between asthma ED visits and inspection scores: asthma ED visits increased more than 1 year before a failed HUD inspection. They also found that asthma ED visits were not elevated at housing units that passed inspection. Using asthma ED visits to predict failed housing inspections produced a specificity rate of 92.3% in an adjusted model, Dr. Samuels noted.

“This approach represents a novel method of early identification of dangerous housing conditions, which could aid in the prevention of asthma-related morbidity and mortality,” Dr. Samuels said.

The investigators noted that, of the parcels with the top three incidence rates of asthma ED visits, “all of them have been closed or demolished.”

In addition to limiting exposure of patients with asthma to the allergens of mold, mice and rats, and cockroaches, improving poor-quality housing earlier could help asthma by reducing stress, she said.

“There is also an increasing evidence base that psychosocial stress increases the risk of asthma attacks, and it’s therefore possible that living in poor housing conditions – often highly stressful situations – drives exacerbation risk via this pathway,” she said. “Synergistic effects between these pathways are also possible or even likely.”

Neeta Thakur, MD, associate professor of medicine at the University of California, San Francisco, who researches asthma, said the findings could lead to a strategy for improving poor-quality housing more quickly. As it is, inspections are too infrequent, often prompted by resident complaints.

“Once the complaints get to a certain threshold, then there might be an inspection that happens, and if there is a periodic review of the buildings, they often happen few and far between,” she said. “We could actually use some of the information that we’re already getting from something like ED visits and see if there is a pattern.”

An important follow-up would be to see whether asthma outcomes improve after housing deficiencies are addressed and whether the predictive capacity of ED visits occurs in other places.

“Would you then see a decline in the ED visit rates from individuals living in those buildings?” Dr. Thakur said. “It’s important to find a leading indicator, but you want to be sure that that leading indicator is useful as something that can be intervened upon.”

Dr. Samuels and Dr. Thakur have reported no relevant financial relationships.

 

 

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

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