A 48-year-old insurance executive is offered the option of several health insurance packages at the time of a promotion. He is healthy and a non-smoker; both his parents are alive and well; and he takes only vitamins and fish oil supplements on a regular basis. His levels of total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol are all in the normal range, as is his blood pressure. He plans to purchase the lowest price policy, but wants to know if he should also get a stress test to best guide his care.

GUIDELINES RECOMMEND AGAINST TESTING

Patients who are at low risk of disease and without symptoms should not undergo cardiac stress testing. The test is unlikely to be helpful in these patients and may expose them to harm unnecessarily. Cardiac stress testing such as exercise electrocardiography is most useful in patients who have chest pain and shortness of breath on exertion, to look for underlying cardiovascular disease. Despite this, the test is often used inappropriately as part of a routine health evaluation in low-risk, asymptomatic people, such as this patient.

Recent high-quality guidelines address exercise electrocardiography as a screening test for cardiovascular disease in asymptomatic, low-risk adults.

The US Preventive Services Task Force 2012 guideline¹ recommends against screening with exercise electrocardiography for predicting coronary heart disease events in adults with no symptoms and at low risk of these events. A systematic review found no data from randomized controlled trials or prospective cohort studies of this test to screen asymptomatic adults compared with no screening.²

The American Academy of Family Physicians (AAFP) 2012 guideline³ recommends against routine screening with exercise electrocardiography either for the presence of severe coronary artery stenosis or for predicting coronary events in adults at low risk. The AAFP guideline notes that there is moderate or high certainty of no net benefit or that the harms outweigh the benefits of exercise electrocardiography in adults at low risk and without symptoms.

The 2010 joint guideline of the American College of Cardiology and the American Heart Association⁴ does not comment on the role of screening exercise electrocardiography in low-risk asymptomatic adults, but states that a physician may consider ordering exercise electrocardiography in asymptomatic adults at intermediate risk of coronary heart disease. The guideline recommends that the individual physician decide whether screening exercise electrocardiography is warranted in a patient at intermediate risk.

The Choosing Wisely initiative

As part of the Choosing Wisely initiative of the American Board of Internal Medicine Foundation, a number of medical specialty societies have published lists of recommendations and issues that physicians and patients should question and discuss. Cardiac stress testing in low-risk asymptomatic patients is on the list of a number of organizations, including the American College of Physicians, the American College of Cardiology, the AAFP, and the American Society of Nuclear Cardiology. These lists can be found at www.choosingwisely.org.

POSSIBLE HARM ASSOCIATED WITH CARDIAC STRESS TESTING

The overall risk of sudden cardiac death or an event that requires hospitalization during exercise electrocardiography is very small, estimated to be 1 per 10,000 tests, and the risk is probably even less in patients at low risk.⁵ But the risk of potential downstream harm from additional testing or interventions may be greater than direct harm. Still, no study has yet assessed harm associated with follow-up testing or interventions after screening with exercise electrocardiography.

On the basis of large, population-based registries that include symptomatic persons, the risk of any serious adverse event as a result of angiography is about 1.7%; this includes a 0.1% risk of death, a 0.05% risk of myocardial infarction, a 0.07% risk of stroke, and a 0.4% risk of arrhythmia.⁶ In addition, coronary angiography is associated with an average effective radiation dose of 7 mSv and myocardial perfusion imaging with a dose of 15.6 mSv.⁷ These are approximately two times and five times the amount of radiation an average person in the United States receives per year from exposure to ambient radiation (3 mSv).

Several studies that included symptomatic and asymptomatic patients who had undergone angiography reported that between 39% and 85% of patients had no coronary artery disease. This means that many patients were subjected to the risks of invasive testing and treatment without the possibility of benefit. Patients who receive lipid-lowering therapy or aspirin because of an abnormal exercise electrocardiogram are also exposed to the risks related to those interventions.

THE CLINICAL BOTTOM LINE

On the basis of current data, the insurance executive should not get a stress test because the results of the test are unlikely to have an impact on his medical management, are unlikely to improve his clinical outcome, and carry a small risk of harm. Low-risk, asymptomatic people with a positive stress test have the same mortality rate as those who have a negative stress test, and its usefulness beyond traditional risk-factor assessment in motivating patients and guiding therapy has not been established.⁸ In addition, the rate of false-positive results with exercise stress testing is as high as 71%.⁹ Although the risk of an adverse event from the initial stress test is low, ie, 1 serious event in 10,000 tests, the risk of subsequent cardiac catheterization after a positive test is significantly higher, ie, 170 serious events in 10,000 tests. For these reasons, the potential harm of exercise electrocardiography outweighs the benefits in this patient.

A 48-year-old insurance executive is offered the option of several health insurance packages at the time of a promotion. He is healthy and a non-smoker; both his parents are alive and well; and he takes only vitamins and fish oil supplements on a regular basis. His levels of total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol are all in the normal range, as is his blood pressure. He plans to purchase the lowest price policy, but wants to know if he should also get a stress test to best guide his care.

GUIDELINES RECOMMEND AGAINST TESTING

Patients who are at low risk of disease and without symptoms should not undergo cardiac stress testing. The test is unlikely to be helpful in these patients and may expose them to harm unnecessarily. Cardiac stress testing such as exercise electrocardiography is most useful in patients who have chest pain and shortness of breath on exertion, to look for underlying cardiovascular disease. Despite this, the test is often used inappropriately as part of a routine health evaluation in low-risk, asymptomatic people, such as this patient.

Recent high-quality guidelines address exercise electrocardiography as a screening test for cardiovascular disease in asymptomatic, low-risk adults.

The US Preventive Services Task Force 2012 guideline¹ recommends against screening with exercise electrocardiography for predicting coronary heart disease events in adults with no symptoms and at low risk of these events. A systematic review found no data from randomized controlled trials or prospective cohort studies of this test to screen asymptomatic adults compared with no screening.²

The American Academy of Family Physicians (AAFP) 2012 guideline³ recommends against routine screening with exercise electrocardiography either for the presence of severe coronary artery stenosis or for predicting coronary events in adults at low risk. The AAFP guideline notes that there is moderate or high certainty of no net benefit or that the harms outweigh the benefits of exercise electrocardiography in adults at low risk and without symptoms.

The 2010 joint guideline of the American College of Cardiology and the American Heart Association⁴ does not comment on the role of screening exercise electrocardiography in low-risk asymptomatic adults, but states that a physician may consider ordering exercise electrocardiography in asymptomatic adults at intermediate risk of coronary heart disease. The guideline recommends that the individual physician decide whether screening exercise electrocardiography is warranted in a patient at intermediate risk.

The Choosing Wisely initiative

As part of the Choosing Wisely initiative of the American Board of Internal Medicine Foundation, a number of medical specialty societies have published lists of recommendations and issues that physicians and patients should question and discuss. Cardiac stress testing in low-risk asymptomatic patients is on the list of a number of organizations, including the American College of Physicians, the American College of Cardiology, the AAFP, and the American Society of Nuclear Cardiology. These lists can be found at www.choosingwisely.org.

POSSIBLE HARM ASSOCIATED WITH CARDIAC STRESS TESTING

The overall risk of sudden cardiac death or an event that requires hospitalization during exercise electrocardiography is very small, estimated to be 1 per 10,000 tests, and the risk is probably even less in patients at low risk.⁵ But the risk of potential downstream harm from additional testing or interventions may be greater than direct harm. Still, no study has yet assessed harm associated with follow-up testing or interventions after screening with exercise electrocardiography.

On the basis of large, population-based registries that include symptomatic persons, the risk of any serious adverse event as a result of angiography is about 1.7%; this includes a 0.1% risk of death, a 0.05% risk of myocardial infarction, a 0.07% risk of stroke, and a 0.4% risk of arrhythmia.⁶ In addition, coronary angiography is associated with an average effective radiation dose of 7 mSv and myocardial perfusion imaging with a dose of 15.6 mSv.⁷ These are approximately two times and five times the amount of radiation an average person in the United States receives per year from exposure to ambient radiation (3 mSv).

Several studies that included symptomatic and asymptomatic patients who had undergone angiography reported that between 39% and 85% of patients had no coronary artery disease. This means that many patients were subjected to the risks of invasive testing and treatment without the possibility of benefit. Patients who receive lipid-lowering therapy or aspirin because of an abnormal exercise electrocardiogram are also exposed to the risks related to those interventions.

THE CLINICAL BOTTOM LINE

On the basis of current data, the insurance executive should not get a stress test because the results of the test are unlikely to have an impact on his medical management, are unlikely to improve his clinical outcome, and carry a small risk of harm. Low-risk, asymptomatic people with a positive stress test have the same mortality rate as those who have a negative stress test, and its usefulness beyond traditional risk-factor assessment in motivating patients and guiding therapy has not been established.⁸ In addition, the rate of false-positive results with exercise stress testing is as high as 71%.⁹ Although the risk of an adverse event from the initial stress test is low, ie, 1 serious event in 10,000 tests, the risk of subsequent cardiac catheterization after a positive test is significantly higher, ie, 170 serious events in 10,000 tests. For these reasons, the potential harm of exercise electrocardiography outweighs the benefits in this patient.

A 48-year-old insurance executive is offered the option of several health insurance packages at the time of a promotion. He is healthy and a non-smoker; both his parents are alive and well; and he takes only vitamins and fish oil supplements on a regular basis. His levels of total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol are all in the normal range, as is his blood pressure. He plans to purchase the lowest price policy, but wants to know if he should also get a stress test to best guide his care.

GUIDELINES RECOMMEND AGAINST TESTING

Patients who are at low risk of disease and without symptoms should not undergo cardiac stress testing. The test is unlikely to be helpful in these patients and may expose them to harm unnecessarily. Cardiac stress testing such as exercise electrocardiography is most useful in patients who have chest pain and shortness of breath on exertion, to look for underlying cardiovascular disease. Despite this, the test is often used inappropriately as part of a routine health evaluation in low-risk, asymptomatic people, such as this patient.

Recent high-quality guidelines address exercise electrocardiography as a screening test for cardiovascular disease in asymptomatic, low-risk adults.

The US Preventive Services Task Force 2012 guideline¹ recommends against screening with exercise electrocardiography for predicting coronary heart disease events in adults with no symptoms and at low risk of these events. A systematic review found no data from randomized controlled trials or prospective cohort studies of this test to screen asymptomatic adults compared with no screening.²

The American Academy of Family Physicians (AAFP) 2012 guideline³ recommends against routine screening with exercise electrocardiography either for the presence of severe coronary artery stenosis or for predicting coronary events in adults at low risk. The AAFP guideline notes that there is moderate or high certainty of no net benefit or that the harms outweigh the benefits of exercise electrocardiography in adults at low risk and without symptoms.

The 2010 joint guideline of the American College of Cardiology and the American Heart Association⁴ does not comment on the role of screening exercise electrocardiography in low-risk asymptomatic adults, but states that a physician may consider ordering exercise electrocardiography in asymptomatic adults at intermediate risk of coronary heart disease. The guideline recommends that the individual physician decide whether screening exercise electrocardiography is warranted in a patient at intermediate risk.

The Choosing Wisely initiative

As part of the Choosing Wisely initiative of the American Board of Internal Medicine Foundation, a number of medical specialty societies have published lists of recommendations and issues that physicians and patients should question and discuss. Cardiac stress testing in low-risk asymptomatic patients is on the list of a number of organizations, including the American College of Physicians, the American College of Cardiology, the AAFP, and the American Society of Nuclear Cardiology. These lists can be found at www.choosingwisely.org.

POSSIBLE HARM ASSOCIATED WITH CARDIAC STRESS TESTING

The overall risk of sudden cardiac death or an event that requires hospitalization during exercise electrocardiography is very small, estimated to be 1 per 10,000 tests, and the risk is probably even less in patients at low risk.⁵ But the risk of potential downstream harm from additional testing or interventions may be greater than direct harm. Still, no study has yet assessed harm associated with follow-up testing or interventions after screening with exercise electrocardiography.

On the basis of large, population-based registries that include symptomatic persons, the risk of any serious adverse event as a result of angiography is about 1.7%; this includes a 0.1% risk of death, a 0.05% risk of myocardial infarction, a 0.07% risk of stroke, and a 0.4% risk of arrhythmia.⁶ In addition, coronary angiography is associated with an average effective radiation dose of 7 mSv and myocardial perfusion imaging with a dose of 15.6 mSv.⁷ These are approximately two times and five times the amount of radiation an average person in the United States receives per year from exposure to ambient radiation (3 mSv).

Several studies that included symptomatic and asymptomatic patients who had undergone angiography reported that between 39% and 85% of patients had no coronary artery disease. This means that many patients were subjected to the risks of invasive testing and treatment without the possibility of benefit. Patients who receive lipid-lowering therapy or aspirin because of an abnormal exercise electrocardiogram are also exposed to the risks related to those interventions.

THE CLINICAL BOTTOM LINE

On the basis of current data, the insurance executive should not get a stress test because the results of the test are unlikely to have an impact on his medical management, are unlikely to improve his clinical outcome, and carry a small risk of harm. Low-risk, asymptomatic people with a positive stress test have the same mortality rate as those who have a negative stress test, and its usefulness beyond traditional risk-factor assessment in motivating patients and guiding therapy has not been established.⁸ In addition, the rate of false-positive results with exercise stress testing is as high as 71%.⁹ Although the risk of an adverse event from the initial stress test is low, ie, 1 serious event in 10,000 tests, the risk of subsequent cardiac catheterization after a positive test is significantly higher, ie, 170 serious events in 10,000 tests. For these reasons, the potential harm of exercise electrocardiography outweighs the benefits in this patient.

It’s simple. It’s obvious. None of us would like to be known as someone who orders diagnostic tests in a careless or stupid manner. And none of us order that way—just ask us! Yet, when critically evaluated, someone is ordering slews of unnecessary or inappropriate tests. In my own hospital we saved about $100,000 last year by putting “hard stops” on duplicated blood tests that were ordered too frequently to be of clinical value. This is an obvious and easily enacted intervention, but it is just the tip of the testing iceberg.

As technology advances, our testing practices must change. For example, the ventilation-perfusion nuclear scan is now seldom the test of choice when evaluating a patient with possible pulmonary embolism. However, it still has a role for experienced clinicians evaluating selected patients who have unexplained dyspnea or pulmonary hypertension. There is value in knowing the old as well as new testing modalities.

We like to think we practice evidence-based diagnostic testing. We talk about the gold-standard value of randomized controlled trials and using published data on pretest and posttest diagnostic likelihoods to assist us in choosing the appropriate test. However, the individual patient in front of us may have comorbidities that would have excluded her from the randomized trials. Who knows if my diagnostic acumen in determining the pretest likelihood of disease is better or worse than that of the clinicians who published the paper on the utility of that test? Sometimes choosing a test is not so simple.

Much of my clinical decision-making occurs in a gray zone of uncertainty. Rarely will a single test provide an indisputable diagnosis. So, I may bristle when someone, often for cost reasons, questions the necessity of a diagnostic test that I have ordered to help me understand a clinical problem in a specific patient.

Nevertheless, as Dr. Patrick Alguire points out in an editorial, the frequent use of sophisticated and expensive testing in the United States has not resulted in better clinical outcomes. And as Drs. Alraies and Buitrago et al discuss in letters to the editor, even relatively simple and minimally invasive tests can result in dire, unexpected outcomes. The choice of test matters to individual patients and to the health care system as a whole.

I do not minimize the financial impact of inappropriate testing, but in the clinic I am a doctor, not a businessman. I am far more swayed by clinical arguments than financial ones when making decisions for the patient on the examining table in front of me. Despite the general examples I provided above as to why regulated, cookbook approaches to test-ordering may lead to suboptimal care and physician and patient dissatisfaction (albeit while decreasing costs), sometimes ordering certain tests in certain circumstances just doesn’t make sense. Yet, there are many questionable test and scenario pairings that are ingrained in common practice. Some we learned during our training but have become less useful in light of new knowledge, some we may have adopted because of anecdotal experiences, and some are “demanded” by our patients. It is these that we hope to help expunge from routine clinical care.

In this issue of the Journal  we are initiating a new series within our 1-Minute Consults, called Smart Testing. We are joining the efforts of the American College of Physicians (ACP) in educating physicians about reasons to avoid ordering frequently misused tests—tests that may add more harm, cost, or both than clinical utility to the care of our patients. The ACP also has an educational initiative called “High Value Care” that can be accessed (at no cost) at http://hvc.acponline.org/index.html. We at the Journal are very pleased to be working with physicians at the ACP to offer you this peer-reviewed series of patient vignettes that will focus, in an evidence-based and common-sense way, on the clinical value of selected tests in specific scenarios. Next month we will also be presenting a commentary on the impact that “defensive medicine” plays in test ordering and malpractice case decisions.

The tests and scenarios to be presented are chosen in clinician group discussions. Some of the tests have also been identified by specialty societies as providing limited value to patients. In selecting the topics, we pick common scenarios, realizing that there can often (always?) be some situational nuance that negates the accompanying discussion. We are not expecting to throw light on those nuanced zones of uncertainty, but we do hope to change test-ordering behaviors in situations in which there is a smart—and a not-so-smart—way to pursue a diagnosis.

It’s simple. It’s obvious. None of us would like to be known as someone who orders diagnostic tests in a careless or stupid manner. And none of us order that way—just ask us! Yet, when critically evaluated, someone is ordering slews of unnecessary or inappropriate tests. In my own hospital we saved about $100,000 last year by putting “hard stops” on duplicated blood tests that were ordered too frequently to be of clinical value. This is an obvious and easily enacted intervention, but it is just the tip of the testing iceberg.

As technology advances, our testing practices must change. For example, the ventilation-perfusion nuclear scan is now seldom the test of choice when evaluating a patient with possible pulmonary embolism. However, it still has a role for experienced clinicians evaluating selected patients who have unexplained dyspnea or pulmonary hypertension. There is value in knowing the old as well as new testing modalities.

We like to think we practice evidence-based diagnostic testing. We talk about the gold-standard value of randomized controlled trials and using published data on pretest and posttest diagnostic likelihoods to assist us in choosing the appropriate test. However, the individual patient in front of us may have comorbidities that would have excluded her from the randomized trials. Who knows if my diagnostic acumen in determining the pretest likelihood of disease is better or worse than that of the clinicians who published the paper on the utility of that test? Sometimes choosing a test is not so simple.

Much of my clinical decision-making occurs in a gray zone of uncertainty. Rarely will a single test provide an indisputable diagnosis. So, I may bristle when someone, often for cost reasons, questions the necessity of a diagnostic test that I have ordered to help me understand a clinical problem in a specific patient.

Nevertheless, as Dr. Patrick Alguire points out in an editorial, the frequent use of sophisticated and expensive testing in the United States has not resulted in better clinical outcomes. And as Drs. Alraies and Buitrago et al discuss in letters to the editor, even relatively simple and minimally invasive tests can result in dire, unexpected outcomes. The choice of test matters to individual patients and to the health care system as a whole.

I do not minimize the financial impact of inappropriate testing, but in the clinic I am a doctor, not a businessman. I am far more swayed by clinical arguments than financial ones when making decisions for the patient on the examining table in front of me. Despite the general examples I provided above as to why regulated, cookbook approaches to test-ordering may lead to suboptimal care and physician and patient dissatisfaction (albeit while decreasing costs), sometimes ordering certain tests in certain circumstances just doesn’t make sense. Yet, there are many questionable test and scenario pairings that are ingrained in common practice. Some we learned during our training but have become less useful in light of new knowledge, some we may have adopted because of anecdotal experiences, and some are “demanded” by our patients. It is these that we hope to help expunge from routine clinical care.

In this issue of the Journal  we are initiating a new series within our 1-Minute Consults, called Smart Testing. We are joining the efforts of the American College of Physicians (ACP) in educating physicians about reasons to avoid ordering frequently misused tests—tests that may add more harm, cost, or both than clinical utility to the care of our patients. The ACP also has an educational initiative called “High Value Care” that can be accessed (at no cost) at http://hvc.acponline.org/index.html. We at the Journal are very pleased to be working with physicians at the ACP to offer you this peer-reviewed series of patient vignettes that will focus, in an evidence-based and common-sense way, on the clinical value of selected tests in specific scenarios. Next month we will also be presenting a commentary on the impact that “defensive medicine” plays in test ordering and malpractice case decisions.

The tests and scenarios to be presented are chosen in clinician group discussions. Some of the tests have also been identified by specialty societies as providing limited value to patients. In selecting the topics, we pick common scenarios, realizing that there can often (always?) be some situational nuance that negates the accompanying discussion. We are not expecting to throw light on those nuanced zones of uncertainty, but we do hope to change test-ordering behaviors in situations in which there is a smart—and a not-so-smart—way to pursue a diagnosis.

It’s simple. It’s obvious. None of us would like to be known as someone who orders diagnostic tests in a careless or stupid manner. And none of us order that way—just ask us! Yet, when critically evaluated, someone is ordering slews of unnecessary or inappropriate tests. In my own hospital we saved about $100,000 last year by putting “hard stops” on duplicated blood tests that were ordered too frequently to be of clinical value. This is an obvious and easily enacted intervention, but it is just the tip of the testing iceberg.

As technology advances, our testing practices must change. For example, the ventilation-perfusion nuclear scan is now seldom the test of choice when evaluating a patient with possible pulmonary embolism. However, it still has a role for experienced clinicians evaluating selected patients who have unexplained dyspnea or pulmonary hypertension. There is value in knowing the old as well as new testing modalities.

We like to think we practice evidence-based diagnostic testing. We talk about the gold-standard value of randomized controlled trials and using published data on pretest and posttest diagnostic likelihoods to assist us in choosing the appropriate test. However, the individual patient in front of us may have comorbidities that would have excluded her from the randomized trials. Who knows if my diagnostic acumen in determining the pretest likelihood of disease is better or worse than that of the clinicians who published the paper on the utility of that test? Sometimes choosing a test is not so simple.

Much of my clinical decision-making occurs in a gray zone of uncertainty. Rarely will a single test provide an indisputable diagnosis. So, I may bristle when someone, often for cost reasons, questions the necessity of a diagnostic test that I have ordered to help me understand a clinical problem in a specific patient.

Nevertheless, as Dr. Patrick Alguire points out in an editorial, the frequent use of sophisticated and expensive testing in the United States has not resulted in better clinical outcomes. And as Drs. Alraies and Buitrago et al discuss in letters to the editor, even relatively simple and minimally invasive tests can result in dire, unexpected outcomes. The choice of test matters to individual patients and to the health care system as a whole.

I do not minimize the financial impact of inappropriate testing, but in the clinic I am a doctor, not a businessman. I am far more swayed by clinical arguments than financial ones when making decisions for the patient on the examining table in front of me. Despite the general examples I provided above as to why regulated, cookbook approaches to test-ordering may lead to suboptimal care and physician and patient dissatisfaction (albeit while decreasing costs), sometimes ordering certain tests in certain circumstances just doesn’t make sense. Yet, there are many questionable test and scenario pairings that are ingrained in common practice. Some we learned during our training but have become less useful in light of new knowledge, some we may have adopted because of anecdotal experiences, and some are “demanded” by our patients. It is these that we hope to help expunge from routine clinical care.

In this issue of the Journal  we are initiating a new series within our 1-Minute Consults, called Smart Testing. We are joining the efforts of the American College of Physicians (ACP) in educating physicians about reasons to avoid ordering frequently misused tests—tests that may add more harm, cost, or both than clinical utility to the care of our patients. The ACP also has an educational initiative called “High Value Care” that can be accessed (at no cost) at http://hvc.acponline.org/index.html. We at the Journal are very pleased to be working with physicians at the ACP to offer you this peer-reviewed series of patient vignettes that will focus, in an evidence-based and common-sense way, on the clinical value of selected tests in specific scenarios. Next month we will also be presenting a commentary on the impact that “defensive medicine” plays in test ordering and malpractice case decisions.

The tests and scenarios to be presented are chosen in clinician group discussions. Some of the tests have also been identified by specialty societies as providing limited value to patients. In selecting the topics, we pick common scenarios, realizing that there can often (always?) be some situational nuance that negates the accompanying discussion. We are not expecting to throw light on those nuanced zones of uncertainty, but we do hope to change test-ordering behaviors in situations in which there is a smart—and a not-so-smart—way to pursue a diagnosis.

Rates of chronic pain and opioid use are significantly higher among soldiers, compared with the general population, a survey of 2,597 Army infantry soldiers showed.

The survey, conducted in 2011 after the soldiers had been deployed from combat in Afghanistan or Iraq, found that 44% of the soldiers reported experiencing chronic pain and 15.1% declared that they had used opioids sometime in the past month.

The survey also found that among those reporting opioid use, 44.1%% said they had experienced only mild or no pain in the past month, while among those with chronic pain, only 23.2% had received opioids in the past month, according to a research letter published online June 30 (JAMA 2014 [doi:10.1001/jamainternmed.2014.2726]).

Those with chronic pain were more likely to be aged over 30 years, to be married or have been married, to be injured during combat, to be in higher-intensity combat, or to have experienced posttraumatic stress disorder or major depressive disorder. Use of opioids was associated with "sex, age 25 years or older, being married, rank, injury during combat, chronic pain, and pain severity," wrote Robin L. Toblin, Ph.D., and colleagues.

"These findings suggest a large unmet need for assessment, management, and treatment of chronic pain and related opioid use and misuse in military personnel after combat deployments," said Dr. Toblin of the center for military psychiatry and neuroscience at the Walter Reed Army Institute of Research in Silver Spring, Md.

An accompanying editorial contrasted the figures for chronic pain and opioid use in the military with those in the general population – 26% and 4%, respectively (JAMA 2014 June 30 [doi:10.1001/jamainternmed.2014.2114]).

"While chronic pain and opioid use have been a long-standing concern of the military leadership, this study is among the first to quantify the impact of recent wars on the prevalence of pain and narcotic use among soldiers," wrote Dr. Wayne B. Jonas of the Samueli Institute in Alexandria, Va., and the Uniformed Services University of the Health Sciences in Bethesda, Md., and Dr. Eric B. Schoomaker, also of the Samueli Institute.

No conflicts of interest were declared.

Rates of chronic pain and opioid use are significantly higher among soldiers, compared with the general population, a survey of 2,597 Army infantry soldiers showed.

The survey, conducted in 2011 after the soldiers had been deployed from combat in Afghanistan or Iraq, found that 44% of the soldiers reported experiencing chronic pain and 15.1% declared that they had used opioids sometime in the past month.

The survey also found that among those reporting opioid use, 44.1%% said they had experienced only mild or no pain in the past month, while among those with chronic pain, only 23.2% had received opioids in the past month, according to a research letter published online June 30 (JAMA 2014 [doi:10.1001/jamainternmed.2014.2726]).

Those with chronic pain were more likely to be aged over 30 years, to be married or have been married, to be injured during combat, to be in higher-intensity combat, or to have experienced posttraumatic stress disorder or major depressive disorder. Use of opioids was associated with "sex, age 25 years or older, being married, rank, injury during combat, chronic pain, and pain severity," wrote Robin L. Toblin, Ph.D., and colleagues.

"These findings suggest a large unmet need for assessment, management, and treatment of chronic pain and related opioid use and misuse in military personnel after combat deployments," said Dr. Toblin of the center for military psychiatry and neuroscience at the Walter Reed Army Institute of Research in Silver Spring, Md.

An accompanying editorial contrasted the figures for chronic pain and opioid use in the military with those in the general population – 26% and 4%, respectively (JAMA 2014 June 30 [doi:10.1001/jamainternmed.2014.2114]).

"While chronic pain and opioid use have been a long-standing concern of the military leadership, this study is among the first to quantify the impact of recent wars on the prevalence of pain and narcotic use among soldiers," wrote Dr. Wayne B. Jonas of the Samueli Institute in Alexandria, Va., and the Uniformed Services University of the Health Sciences in Bethesda, Md., and Dr. Eric B. Schoomaker, also of the Samueli Institute.

No conflicts of interest were declared.

Rates of chronic pain and opioid use are significantly higher among soldiers, compared with the general population, a survey of 2,597 Army infantry soldiers showed.

The survey, conducted in 2011 after the soldiers had been deployed from combat in Afghanistan or Iraq, found that 44% of the soldiers reported experiencing chronic pain and 15.1% declared that they had used opioids sometime in the past month.

The survey also found that among those reporting opioid use, 44.1%% said they had experienced only mild or no pain in the past month, while among those with chronic pain, only 23.2% had received opioids in the past month, according to a research letter published online June 30 (JAMA 2014 [doi:10.1001/jamainternmed.2014.2726]).

Those with chronic pain were more likely to be aged over 30 years, to be married or have been married, to be injured during combat, to be in higher-intensity combat, or to have experienced posttraumatic stress disorder or major depressive disorder. Use of opioids was associated with "sex, age 25 years or older, being married, rank, injury during combat, chronic pain, and pain severity," wrote Robin L. Toblin, Ph.D., and colleagues.

"These findings suggest a large unmet need for assessment, management, and treatment of chronic pain and related opioid use and misuse in military personnel after combat deployments," said Dr. Toblin of the center for military psychiatry and neuroscience at the Walter Reed Army Institute of Research in Silver Spring, Md.

An accompanying editorial contrasted the figures for chronic pain and opioid use in the military with those in the general population – 26% and 4%, respectively (JAMA 2014 June 30 [doi:10.1001/jamainternmed.2014.2114]).

"While chronic pain and opioid use have been a long-standing concern of the military leadership, this study is among the first to quantify the impact of recent wars on the prevalence of pain and narcotic use among soldiers," wrote Dr. Wayne B. Jonas of the Samueli Institute in Alexandria, Va., and the Uniformed Services University of the Health Sciences in Bethesda, Md., and Dr. Eric B. Schoomaker, also of the Samueli Institute.

No conflicts of interest were declared.

HSCs for transplant

Credit: Chad McNeeley

Scientists say they’ve overcome a major hurdle to developing gene therapies for blood disorders.

They found the drug rapamycin could help them bypass the natural defenses of hematopoietic stem cells (HSCs) and deliver therapeutic doses of disease-fighting genes, without compromising HSC function.

The team believes this discovery could lead to more effective and affordable long-term treatments for disorders such as leukemia and sickle cell anemia.

Bruce Torbett, PhD, of The Scripps Research Institute in La Jolla, California, and his colleagues reported their findings in Blood.

Past research showed that HIV vectors can deliver genes to HSCs. However, when scientists extract HSCs from the body for gene therapy, HIV vectors are usually able to deliver genes to about 30% to 40% of the cells.

For leukemia, leukodystrophy, or genetic diseases where treatment requires a reasonable number of healthy cells derived from stem cells, this number may be too low for therapeutic purposes.

This limitation prompted Dr Torbett and his colleagues to test whether rapamycin could improve delivery of a gene to HSCs. Rapamycin was selected based on its ability to control virus entry and slow cell growth.

The researchers began by isolating stem cells from cord blood samples. They exposed the HSCs to rapamycin and HIV vectors engineered to deliver a gene for a green florescent protein. This fluorescence provided a visual marker that helped the team track gene delivery.

They saw a big difference in both mouse and human stem cells treated with rapamycin, where therapeutic genes were inserted into up to 80% of cells. This property had never been connected to rapamycin before.

The researchers also found that rapamycin can keep HSCs from differentiating as quickly when taken out of the body for gene therapy.

“We wanted to make sure the conditions we will use preserve stem cells, so if we transplant them back into our animal models, they act just like the original stem cells,” Dr Torbett said. “We showed that, in 2 sets of animal models, stem cells remain and produce gene-modified cells.”

The scientists hope these methods could someday be useful in the clinic.

“Our methods could reduce costs and the amount of preparation that goes into modifying blood stem cells using viral vector gene therapy,” said Cathy Wang, also of The Scripps Research Institute. “It would make gene therapy accessible to a lot more patients.”

She said the team’s next steps are to carry out preclinical studies using rapamycin with stem cells in other animal models and then test the method in humans. The researchers are also working to delineate the dual pathways of rapamycin’s mechanism of action in HSCs.

HSCs for transplant

Credit: Chad McNeeley

Scientists say they’ve overcome a major hurdle to developing gene therapies for blood disorders.

They found the drug rapamycin could help them bypass the natural defenses of hematopoietic stem cells (HSCs) and deliver therapeutic doses of disease-fighting genes, without compromising HSC function.

The team believes this discovery could lead to more effective and affordable long-term treatments for disorders such as leukemia and sickle cell anemia.

Bruce Torbett, PhD, of The Scripps Research Institute in La Jolla, California, and his colleagues reported their findings in Blood.

Past research showed that HIV vectors can deliver genes to HSCs. However, when scientists extract HSCs from the body for gene therapy, HIV vectors are usually able to deliver genes to about 30% to 40% of the cells.

For leukemia, leukodystrophy, or genetic diseases where treatment requires a reasonable number of healthy cells derived from stem cells, this number may be too low for therapeutic purposes.

This limitation prompted Dr Torbett and his colleagues to test whether rapamycin could improve delivery of a gene to HSCs. Rapamycin was selected based on its ability to control virus entry and slow cell growth.

The researchers began by isolating stem cells from cord blood samples. They exposed the HSCs to rapamycin and HIV vectors engineered to deliver a gene for a green florescent protein. This fluorescence provided a visual marker that helped the team track gene delivery.

They saw a big difference in both mouse and human stem cells treated with rapamycin, where therapeutic genes were inserted into up to 80% of cells. This property had never been connected to rapamycin before.

The researchers also found that rapamycin can keep HSCs from differentiating as quickly when taken out of the body for gene therapy.

“We wanted to make sure the conditions we will use preserve stem cells, so if we transplant them back into our animal models, they act just like the original stem cells,” Dr Torbett said. “We showed that, in 2 sets of animal models, stem cells remain and produce gene-modified cells.”

The scientists hope these methods could someday be useful in the clinic.

“Our methods could reduce costs and the amount of preparation that goes into modifying blood stem cells using viral vector gene therapy,” said Cathy Wang, also of The Scripps Research Institute. “It would make gene therapy accessible to a lot more patients.”

She said the team’s next steps are to carry out preclinical studies using rapamycin with stem cells in other animal models and then test the method in humans. The researchers are also working to delineate the dual pathways of rapamycin’s mechanism of action in HSCs.

HSCs for transplant

Credit: Chad McNeeley

Scientists say they’ve overcome a major hurdle to developing gene therapies for blood disorders.

They found the drug rapamycin could help them bypass the natural defenses of hematopoietic stem cells (HSCs) and deliver therapeutic doses of disease-fighting genes, without compromising HSC function.

The team believes this discovery could lead to more effective and affordable long-term treatments for disorders such as leukemia and sickle cell anemia.

Bruce Torbett, PhD, of The Scripps Research Institute in La Jolla, California, and his colleagues reported their findings in Blood.

Past research showed that HIV vectors can deliver genes to HSCs. However, when scientists extract HSCs from the body for gene therapy, HIV vectors are usually able to deliver genes to about 30% to 40% of the cells.

For leukemia, leukodystrophy, or genetic diseases where treatment requires a reasonable number of healthy cells derived from stem cells, this number may be too low for therapeutic purposes.

This limitation prompted Dr Torbett and his colleagues to test whether rapamycin could improve delivery of a gene to HSCs. Rapamycin was selected based on its ability to control virus entry and slow cell growth.

The researchers began by isolating stem cells from cord blood samples. They exposed the HSCs to rapamycin and HIV vectors engineered to deliver a gene for a green florescent protein. This fluorescence provided a visual marker that helped the team track gene delivery.

They saw a big difference in both mouse and human stem cells treated with rapamycin, where therapeutic genes were inserted into up to 80% of cells. This property had never been connected to rapamycin before.

The researchers also found that rapamycin can keep HSCs from differentiating as quickly when taken out of the body for gene therapy.

“We wanted to make sure the conditions we will use preserve stem cells, so if we transplant them back into our animal models, they act just like the original stem cells,” Dr Torbett said. “We showed that, in 2 sets of animal models, stem cells remain and produce gene-modified cells.”

The scientists hope these methods could someday be useful in the clinic.

“Our methods could reduce costs and the amount of preparation that goes into modifying blood stem cells using viral vector gene therapy,” said Cathy Wang, also of The Scripps Research Institute. “It would make gene therapy accessible to a lot more patients.”

She said the team’s next steps are to carry out preclinical studies using rapamycin with stem cells in other animal models and then test the method in humans. The researchers are also working to delineate the dual pathways of rapamycin’s mechanism of action in HSCs.

Doctor examining patient

Credit: Logan Tuttle

A new study suggests videoconferencing with family and friends can lower stress for pediatric patients who are hospitalized for an extended period.

UC Davis Children’s Hospital provides these patients with laptops, webcams, and secure Internet connections for videoconferencing.

And anecdotal accounts have suggested the service, called Family-Link, benefits patients. But researchers wanted more concrete evidence that Family-Link can reduce anxiety.

To that end, James Marcin, MD, and his colleagues studied 367 children who were hospitalized at UC Davis for at least 4 days.

Two hundred and thirty-two patients took advantage of the videoconferencing service, and 135 did not. The researchers used the Parent-Guardian Stress Survey to assess the children’s anxiety levels, both at admission and discharge.

The survey included 4 question groups centered on each child’s behavior and emotions, staff communication, sights and sounds, and the child’s appearance. Parents/guardians were asked whether the child exhibited a variety of behaviors, such as being demanding, frightened, angry, or confused.

The survey also included questions about the impact of monitoring equipment on stress levels and the staff’s ability to communicate important details about the child’s care.

Overall, children who used Family-Link experienced a greater reduction in stress than children who did not use the service.

The researchers were surprised to find this effect was even more pronounced for children who lived closer to the hospital and had shorter hospitalizations. This group experienced a 37% stress reduction when using Family-Link.

“This study shows that we have another tool to help children during their hospital stays,” said Nikki Yang, first author on the study. “The improvement in stress scores shows that Family-Link is really helping many children and might possibly be improving outcomes.”

Yang and her colleagues reported these findings in Pediatrics.

Doctor examining patient

Credit: Logan Tuttle

A new study suggests videoconferencing with family and friends can lower stress for pediatric patients who are hospitalized for an extended period.

UC Davis Children’s Hospital provides these patients with laptops, webcams, and secure Internet connections for videoconferencing.

And anecdotal accounts have suggested the service, called Family-Link, benefits patients. But researchers wanted more concrete evidence that Family-Link can reduce anxiety.

To that end, James Marcin, MD, and his colleagues studied 367 children who were hospitalized at UC Davis for at least 4 days.

Two hundred and thirty-two patients took advantage of the videoconferencing service, and 135 did not. The researchers used the Parent-Guardian Stress Survey to assess the children’s anxiety levels, both at admission and discharge.

The survey included 4 question groups centered on each child’s behavior and emotions, staff communication, sights and sounds, and the child’s appearance. Parents/guardians were asked whether the child exhibited a variety of behaviors, such as being demanding, frightened, angry, or confused.

The survey also included questions about the impact of monitoring equipment on stress levels and the staff’s ability to communicate important details about the child’s care.

Overall, children who used Family-Link experienced a greater reduction in stress than children who did not use the service.

The researchers were surprised to find this effect was even more pronounced for children who lived closer to the hospital and had shorter hospitalizations. This group experienced a 37% stress reduction when using Family-Link.

“This study shows that we have another tool to help children during their hospital stays,” said Nikki Yang, first author on the study. “The improvement in stress scores shows that Family-Link is really helping many children and might possibly be improving outcomes.”

Yang and her colleagues reported these findings in Pediatrics.

Doctor examining patient

Credit: Logan Tuttle

A new study suggests videoconferencing with family and friends can lower stress for pediatric patients who are hospitalized for an extended period.

UC Davis Children’s Hospital provides these patients with laptops, webcams, and secure Internet connections for videoconferencing.

And anecdotal accounts have suggested the service, called Family-Link, benefits patients. But researchers wanted more concrete evidence that Family-Link can reduce anxiety.

To that end, James Marcin, MD, and his colleagues studied 367 children who were hospitalized at UC Davis for at least 4 days.

Two hundred and thirty-two patients took advantage of the videoconferencing service, and 135 did not. The researchers used the Parent-Guardian Stress Survey to assess the children’s anxiety levels, both at admission and discharge.

The survey included 4 question groups centered on each child’s behavior and emotions, staff communication, sights and sounds, and the child’s appearance. Parents/guardians were asked whether the child exhibited a variety of behaviors, such as being demanding, frightened, angry, or confused.

The survey also included questions about the impact of monitoring equipment on stress levels and the staff’s ability to communicate important details about the child’s care.

Overall, children who used Family-Link experienced a greater reduction in stress than children who did not use the service.

The researchers were surprised to find this effect was even more pronounced for children who lived closer to the hospital and had shorter hospitalizations. This group experienced a 37% stress reduction when using Family-Link.

“This study shows that we have another tool to help children during their hospital stays,” said Nikki Yang, first author on the study. “The improvement in stress scores shows that Family-Link is really helping many children and might possibly be improving outcomes.”

Yang and her colleagues reported these findings in Pediatrics.

Monoclonal antibodies

Credit: Linda Bartlett

The anti-CD20 antibody ofatumumab (Arzerra) has failed to meet the primary endpoint in two phase 3 trials, according to the companies developing the drug.

Ofatumumab failed to improve progression-free survival (PFS) when compared to physicians’ choice in patients with bulky, fludarabine-refractory chronic lymphocytic leukemia (CLL).

Likewise, ofatumumab plus chemotherapy failed to improve PFS when compared to rituximab plus chemotherapy in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

GlaxoSmithKline (GSK) and Genmab recently announced these headline results but said the full analyses of safety and efficacy data are underway and will be completed in the coming months.

However, based on these early results, the companies said they are unlikely to pursue regulatory filings for ofatumumab in either indication.

CLL trial

In the OMB114242 study, researchers enrolled 122 patients with bulky, fludarabine-refractory CLL. Patients were randomized to receive ofatumumab or physicians’ choice (2:1).

Patients randomized to ofatumumab received an initial dose of 300 mg, followed 1 week later by 2000 mg once weekly for 7 weeks, followed 4 weeks later by 1 infusion of 2000 mg every 4 weeks, for a total treatment duration of 6 to 12 months. Patients in the physicians’ choice arm received a treatment regimen chosen by a physician for up to 6 months.

The primary endpoint was PFS, and secondary objectives were to evaluate response, overall survival, safety, tolerability, and health-related quality of life.

The median PFS, as assessed by an independent review committee, was 5.36 months for ofatumumab and 3.61 months for physicians’ choice (hazard ratio 0.79, P=0.267).

“It was our priority to share this result with the scientific community as soon it became available,” said Rafael Amado, MD, Head of Oncology R&D at GSK. “We will now work to further analyze the data and to better understand the totality of the efficacy and safety findings.”

This study was conducted to meet the requirements from the European Commission for the conditional approval of ofatumumab for the treatment of CLL in patients who are refractory to fludarabine and alemtuzumab. The current indications in the European Union and the United States do not include bulky, fludarabine-refractory CLL patients.

“Although ofatumumab performed broadly in line with previous data, today’s result is disappointing,” said Jan van de Winkel, PhD, Chief Executive Officer of Genmab. “Based on this result, we do not anticipate applying for a label expansion for ofatumumab in this specific refractory CLL population.”

DLBCL trial

The ORCHARRD study included 447 patients who were refractory to, or had relapsed following, first-line treatment with rituximab in combination with a chemotherapy regimen containing anthracycline or anthracenedione. Patients were also eligible for autologous stem cell transplant.

Patients were randomized 1:1 to receive 3 cycles of either ofatumumab or rituximab in combination with DHAP (dexamethasone, cytarabine, and cisplatin) salvage chemotherapy. After the third treatment cycle, patients who obtained a complete or partial response received high-dose chemotherapy followed by transplant.

The primary endpoint was PFS. But GSK and Genmab reported no statistically significant difference in PFS between the treatment arms.

There were no differences in adverse events (AEs) leading to treatment discontinuation, grade 3 or higher AEs, or severe AEs between the treatment arms. However, there were more dose interruptions and delays due to infusion reactions and increased serum creatinine in the ofatumumab-plus-chemotherapy arm, which require further analysis.

“We plan to submit detailed data from the ofatumumab ORCHARRD study in DLBCL for presentation at a medical conference later this year, which we hope will provide further clarity on today’s headline results,” Dr van de Winkel said. “Based on [these early] results, we are unlikely to move forward with a regulatory filing.”

Monoclonal antibodies

Credit: Linda Bartlett

The anti-CD20 antibody ofatumumab (Arzerra) has failed to meet the primary endpoint in two phase 3 trials, according to the companies developing the drug.

Ofatumumab failed to improve progression-free survival (PFS) when compared to physicians’ choice in patients with bulky, fludarabine-refractory chronic lymphocytic leukemia (CLL).

Likewise, ofatumumab plus chemotherapy failed to improve PFS when compared to rituximab plus chemotherapy in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

GlaxoSmithKline (GSK) and Genmab recently announced these headline results but said the full analyses of safety and efficacy data are underway and will be completed in the coming months.

However, based on these early results, the companies said they are unlikely to pursue regulatory filings for ofatumumab in either indication.

CLL trial

In the OMB114242 study, researchers enrolled 122 patients with bulky, fludarabine-refractory CLL. Patients were randomized to receive ofatumumab or physicians’ choice (2:1).

Patients randomized to ofatumumab received an initial dose of 300 mg, followed 1 week later by 2000 mg once weekly for 7 weeks, followed 4 weeks later by 1 infusion of 2000 mg every 4 weeks, for a total treatment duration of 6 to 12 months. Patients in the physicians’ choice arm received a treatment regimen chosen by a physician for up to 6 months.

The primary endpoint was PFS, and secondary objectives were to evaluate response, overall survival, safety, tolerability, and health-related quality of life.

The median PFS, as assessed by an independent review committee, was 5.36 months for ofatumumab and 3.61 months for physicians’ choice (hazard ratio 0.79, P=0.267).

“It was our priority to share this result with the scientific community as soon it became available,” said Rafael Amado, MD, Head of Oncology R&D at GSK. “We will now work to further analyze the data and to better understand the totality of the efficacy and safety findings.”

This study was conducted to meet the requirements from the European Commission for the conditional approval of ofatumumab for the treatment of CLL in patients who are refractory to fludarabine and alemtuzumab. The current indications in the European Union and the United States do not include bulky, fludarabine-refractory CLL patients.

“Although ofatumumab performed broadly in line with previous data, today’s result is disappointing,” said Jan van de Winkel, PhD, Chief Executive Officer of Genmab. “Based on this result, we do not anticipate applying for a label expansion for ofatumumab in this specific refractory CLL population.”

DLBCL trial

The ORCHARRD study included 447 patients who were refractory to, or had relapsed following, first-line treatment with rituximab in combination with a chemotherapy regimen containing anthracycline or anthracenedione. Patients were also eligible for autologous stem cell transplant.

Patients were randomized 1:1 to receive 3 cycles of either ofatumumab or rituximab in combination with DHAP (dexamethasone, cytarabine, and cisplatin) salvage chemotherapy. After the third treatment cycle, patients who obtained a complete or partial response received high-dose chemotherapy followed by transplant.

The primary endpoint was PFS. But GSK and Genmab reported no statistically significant difference in PFS between the treatment arms.

There were no differences in adverse events (AEs) leading to treatment discontinuation, grade 3 or higher AEs, or severe AEs between the treatment arms. However, there were more dose interruptions and delays due to infusion reactions and increased serum creatinine in the ofatumumab-plus-chemotherapy arm, which require further analysis.

“We plan to submit detailed data from the ofatumumab ORCHARRD study in DLBCL for presentation at a medical conference later this year, which we hope will provide further clarity on today’s headline results,” Dr van de Winkel said. “Based on [these early] results, we are unlikely to move forward with a regulatory filing.”

Monoclonal antibodies

Credit: Linda Bartlett

The anti-CD20 antibody ofatumumab (Arzerra) has failed to meet the primary endpoint in two phase 3 trials, according to the companies developing the drug.

Ofatumumab failed to improve progression-free survival (PFS) when compared to physicians’ choice in patients with bulky, fludarabine-refractory chronic lymphocytic leukemia (CLL).

Likewise, ofatumumab plus chemotherapy failed to improve PFS when compared to rituximab plus chemotherapy in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

GlaxoSmithKline (GSK) and Genmab recently announced these headline results but said the full analyses of safety and efficacy data are underway and will be completed in the coming months.

However, based on these early results, the companies said they are unlikely to pursue regulatory filings for ofatumumab in either indication.

CLL trial

In the OMB114242 study, researchers enrolled 122 patients with bulky, fludarabine-refractory CLL. Patients were randomized to receive ofatumumab or physicians’ choice (2:1).

Patients randomized to ofatumumab received an initial dose of 300 mg, followed 1 week later by 2000 mg once weekly for 7 weeks, followed 4 weeks later by 1 infusion of 2000 mg every 4 weeks, for a total treatment duration of 6 to 12 months. Patients in the physicians’ choice arm received a treatment regimen chosen by a physician for up to 6 months.

The primary endpoint was PFS, and secondary objectives were to evaluate response, overall survival, safety, tolerability, and health-related quality of life.

The median PFS, as assessed by an independent review committee, was 5.36 months for ofatumumab and 3.61 months for physicians’ choice (hazard ratio 0.79, P=0.267).

“It was our priority to share this result with the scientific community as soon it became available,” said Rafael Amado, MD, Head of Oncology R&D at GSK. “We will now work to further analyze the data and to better understand the totality of the efficacy and safety findings.”

This study was conducted to meet the requirements from the European Commission for the conditional approval of ofatumumab for the treatment of CLL in patients who are refractory to fludarabine and alemtuzumab. The current indications in the European Union and the United States do not include bulky, fludarabine-refractory CLL patients.

“Although ofatumumab performed broadly in line with previous data, today’s result is disappointing,” said Jan van de Winkel, PhD, Chief Executive Officer of Genmab. “Based on this result, we do not anticipate applying for a label expansion for ofatumumab in this specific refractory CLL population.”

DLBCL trial

The ORCHARRD study included 447 patients who were refractory to, or had relapsed following, first-line treatment with rituximab in combination with a chemotherapy regimen containing anthracycline or anthracenedione. Patients were also eligible for autologous stem cell transplant.

Patients were randomized 1:1 to receive 3 cycles of either ofatumumab or rituximab in combination with DHAP (dexamethasone, cytarabine, and cisplatin) salvage chemotherapy. After the third treatment cycle, patients who obtained a complete or partial response received high-dose chemotherapy followed by transplant.

The primary endpoint was PFS. But GSK and Genmab reported no statistically significant difference in PFS between the treatment arms.

There were no differences in adverse events (AEs) leading to treatment discontinuation, grade 3 or higher AEs, or severe AEs between the treatment arms. However, there were more dose interruptions and delays due to infusion reactions and increased serum creatinine in the ofatumumab-plus-chemotherapy arm, which require further analysis.

“We plan to submit detailed data from the ofatumumab ORCHARRD study in DLBCL for presentation at a medical conference later this year, which we hope will provide further clarity on today’s headline results,” Dr van de Winkel said. “Based on [these early] results, we are unlikely to move forward with a regulatory filing.”

Thrombus

Credit: Andre E.X. Brown

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that apixaban (Eliquis) be granted marketing authorization for the treatment and prevention of venous thromboembolism (VTE) in adults.

The European Commission will take the CHMP’s opinion into account when deciding whether to approve the drug for this indication in all 28 European Union member states, plus Iceland and Norway.

The CHMP’s recommendation of apixaban was based on results from the AMPLIFY and AMPLIFY-EXTENSION studies.

The phase 3 AMPLIFY trial enrolled 5395 patients with confirmed, symptomatic deep vein thrombosis (DVT) or pulmonary embolism (PE) requiring treatment for 6 months.

About half of patients (n=2691) were randomized to apixaban, and the other half (n=2704) were randomized to standard of care, which was initial enoxaparin treatment overlapped by warfarin therapy.

The primary efficacy outcome was the composite endpoint of recurrent, symptomatic VTE or VTE-related death. This occurred in 59 patients in the apixaban arm (2.3%) and 71 patients (2.7%) in the standard-therapy arm (P<0.0001 for noninferiority).

The composite endpoint of major bleeding and clinically relevant, nonmajor bleeding occurred in 4.3% of patients in the apixaban arm and 9.7% of patients in the standard-therapy arm (P<0.001).

The phase 3 AMPLIFY-EXTENSION trial included 2486 patients with prior VTE who had completed 6 to 12 months of anticoagulation treatment for DVT or PE.

Eight hundred and forty-two patients were randomized to apixaban at 2.5 mg, 815 were randomized to apixaban at 5 mg, and 829 were randomized to placebo.

The study’s primary efficacy endpoint was recurrent VTE or all-cause death. During the 12-month active study period, these events occurred in 32 patients (3.8%) in the 2.5-mg arm, 34 patients (4.2%) in the 5-mg arm, and 96 patients (11.6%) in the placebo arm. Both apixaban doses were significantly superior to placebo (P<0.001).

The primary safety endpoint was the incidence of major bleeding, which occurred in 2 patients (0.2%) in the 2.5-mg arm, 1 patient (0.1%) in the 5-mg arm, and 4 patients (0.5%) in the placebo arm.

Thrombus

Credit: Andre E.X. Brown

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that apixaban (Eliquis) be granted marketing authorization for the treatment and prevention of venous thromboembolism (VTE) in adults.

The European Commission will take the CHMP’s opinion into account when deciding whether to approve the drug for this indication in all 28 European Union member states, plus Iceland and Norway.

The CHMP’s recommendation of apixaban was based on results from the AMPLIFY and AMPLIFY-EXTENSION studies.

The phase 3 AMPLIFY trial enrolled 5395 patients with confirmed, symptomatic deep vein thrombosis (DVT) or pulmonary embolism (PE) requiring treatment for 6 months.

About half of patients (n=2691) were randomized to apixaban, and the other half (n=2704) were randomized to standard of care, which was initial enoxaparin treatment overlapped by warfarin therapy.

The primary efficacy outcome was the composite endpoint of recurrent, symptomatic VTE or VTE-related death. This occurred in 59 patients in the apixaban arm (2.3%) and 71 patients (2.7%) in the standard-therapy arm (P<0.0001 for noninferiority).

The composite endpoint of major bleeding and clinically relevant, nonmajor bleeding occurred in 4.3% of patients in the apixaban arm and 9.7% of patients in the standard-therapy arm (P<0.001).

The phase 3 AMPLIFY-EXTENSION trial included 2486 patients with prior VTE who had completed 6 to 12 months of anticoagulation treatment for DVT or PE.

Eight hundred and forty-two patients were randomized to apixaban at 2.5 mg, 815 were randomized to apixaban at 5 mg, and 829 were randomized to placebo.

The study’s primary efficacy endpoint was recurrent VTE or all-cause death. During the 12-month active study period, these events occurred in 32 patients (3.8%) in the 2.5-mg arm, 34 patients (4.2%) in the 5-mg arm, and 96 patients (11.6%) in the placebo arm. Both apixaban doses were significantly superior to placebo (P<0.001).

The primary safety endpoint was the incidence of major bleeding, which occurred in 2 patients (0.2%) in the 2.5-mg arm, 1 patient (0.1%) in the 5-mg arm, and 4 patients (0.5%) in the placebo arm.

Thrombus

Credit: Andre E.X. Brown

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that apixaban (Eliquis) be granted marketing authorization for the treatment and prevention of venous thromboembolism (VTE) in adults.

The European Commission will take the CHMP’s opinion into account when deciding whether to approve the drug for this indication in all 28 European Union member states, plus Iceland and Norway.

The CHMP’s recommendation of apixaban was based on results from the AMPLIFY and AMPLIFY-EXTENSION studies.

The phase 3 AMPLIFY trial enrolled 5395 patients with confirmed, symptomatic deep vein thrombosis (DVT) or pulmonary embolism (PE) requiring treatment for 6 months.

About half of patients (n=2691) were randomized to apixaban, and the other half (n=2704) were randomized to standard of care, which was initial enoxaparin treatment overlapped by warfarin therapy.

The primary efficacy outcome was the composite endpoint of recurrent, symptomatic VTE or VTE-related death. This occurred in 59 patients in the apixaban arm (2.3%) and 71 patients (2.7%) in the standard-therapy arm (P<0.0001 for noninferiority).

The composite endpoint of major bleeding and clinically relevant, nonmajor bleeding occurred in 4.3% of patients in the apixaban arm and 9.7% of patients in the standard-therapy arm (P<0.001).

The phase 3 AMPLIFY-EXTENSION trial included 2486 patients with prior VTE who had completed 6 to 12 months of anticoagulation treatment for DVT or PE.

Eight hundred and forty-two patients were randomized to apixaban at 2.5 mg, 815 were randomized to apixaban at 5 mg, and 829 were randomized to placebo.

The study’s primary efficacy endpoint was recurrent VTE or all-cause death. During the 12-month active study period, these events occurred in 32 patients (3.8%) in the 2.5-mg arm, 34 patients (4.2%) in the 5-mg arm, and 96 patients (11.6%) in the placebo arm. Both apixaban doses were significantly superior to placebo (P<0.001).

The primary safety endpoint was the incidence of major bleeding, which occurred in 2 patients (0.2%) in the 2.5-mg arm, 1 patient (0.1%) in the 5-mg arm, and 4 patients (0.5%) in the placebo arm.

Impending stroke chalked up to carpal tunnel syndrome

A WOMAN WENT TO HER PHYSICIAN COMPLAINING OF DIZZINESS, blurred vision, numbness, tingling in her hands and feet, and other symptoms. The physician diagnosed carpal tunnel syndrome. The patient visited her physician a second time, and a day later, suffered a stroke and died.


PLAINTIFF The patient specifically asked her physician if she was having a stroke and her physician told her No.


THE DEFENSE No information about the defense is available.


VERDICT $907,486 Kansas verdict.

COMMENT Certainly carpal tunnel syndrome is not sufficient to explain all of this patient’s symptoms—especially dizziness and blurred vision—but the details on this case are limited. If the patient did in fact express concern about a possible stroke, it was incumbent upon the physician to evaluate carefully and either diagnose that condition or rule it out.

Rather than coming too late, Rx for methadone came too soon

A 34-YEAR-OLD MAN ADDICTED TO OXYCODONE AND OTHER PAIN MEDICATIONS as the result of a work-related injury 10 years earlier sought treatment for his addiction from a family physician (FP) while visiting Kentucky. The patient also was abusing alprazolam. The FP administered a drug test but prescribed methadone, 180 10-mg pills, before receiving the results. The next day, the drug screen returned positive for multiple drugs, including opiates and cannabinoids. The FP’s staff tried to reach the patient, but was unsuccessful. The patient was found dead a few hours later after overdosing on a combination of methadone and alprazolam. Although 64 methadone pills were missing, the patient could not have taken all of them because only a therapeutic level of methadone was found in his system.

PLAINTIFF’S CLAIM The physician should have waited to receive the results of the drug screen before prescribing methadone. Drug Enforcement Administration guidelines allow prescription of methadone for addiction only if a patient is in withdrawal and in the process of being admitted to a treatment facility. There was no proof of withdrawal symptoms.

THE DEFENSE The treatment was reasonable and compassionate. The patient was at fault for abusing narcotics.

VERDICT $204,500 Kentucky verdict.

Could a proper history have spared this patient multiple surgeries?

A 13-YEAR-OLD CAME TO THE EMERGENCY DEPARTMENT (ED) with left knee pain and fever. He was diagnosed with a quadriceps strain and discharged. The next morning the patient still had knee pain and sought treatment from an FP, who diagnosed a sprained knee. At this visit, the patient’s temperature was normal. Three days later, the patient went to another ED with a high fever and knee pain so severe that he couldn’t walk. Blood culture revealed methicillin-resistant Staphylococcus aureus (MRSA) in the knee, which quickly spread. The patient was hospitalized and required 17 surgeries.

PLAINTIFF’S CLAIM The FP should have ordered blood work and recognized the signs of infection. MRSA had been present at least 4 days before it was diagnosed.

THE DEFENSE The patient did not have a diagnosable infection the day the physician saw him and his condition had progressed over the following 3 days.

VERDICT $2.1 million Illinois verdict.

COMMENT This case reminds me of the necessity of obtaining a history of the mechanism of injury for joint pain. Absence of a definite cause should have led to a wider differential diagnosis.

Impending stroke chalked up to carpal tunnel syndrome

A WOMAN WENT TO HER PHYSICIAN COMPLAINING OF DIZZINESS, blurred vision, numbness, tingling in her hands and feet, and other symptoms. The physician diagnosed carpal tunnel syndrome. The patient visited her physician a second time, and a day later, suffered a stroke and died.


PLAINTIFF The patient specifically asked her physician if she was having a stroke and her physician told her No.


THE DEFENSE No information about the defense is available.


VERDICT $907,486 Kansas verdict.

COMMENT Certainly carpal tunnel syndrome is not sufficient to explain all of this patient’s symptoms—especially dizziness and blurred vision—but the details on this case are limited. If the patient did in fact express concern about a possible stroke, it was incumbent upon the physician to evaluate carefully and either diagnose that condition or rule it out.

Rather than coming too late, Rx for methadone came too soon

A 34-YEAR-OLD MAN ADDICTED TO OXYCODONE AND OTHER PAIN MEDICATIONS as the result of a work-related injury 10 years earlier sought treatment for his addiction from a family physician (FP) while visiting Kentucky. The patient also was abusing alprazolam. The FP administered a drug test but prescribed methadone, 180 10-mg pills, before receiving the results. The next day, the drug screen returned positive for multiple drugs, including opiates and cannabinoids. The FP’s staff tried to reach the patient, but was unsuccessful. The patient was found dead a few hours later after overdosing on a combination of methadone and alprazolam. Although 64 methadone pills were missing, the patient could not have taken all of them because only a therapeutic level of methadone was found in his system.

PLAINTIFF’S CLAIM The physician should have waited to receive the results of the drug screen before prescribing methadone. Drug Enforcement Administration guidelines allow prescription of methadone for addiction only if a patient is in withdrawal and in the process of being admitted to a treatment facility. There was no proof of withdrawal symptoms.

THE DEFENSE The treatment was reasonable and compassionate. The patient was at fault for abusing narcotics.

VERDICT $204,500 Kentucky verdict.

Could a proper history have spared this patient multiple surgeries?

A 13-YEAR-OLD CAME TO THE EMERGENCY DEPARTMENT (ED) with left knee pain and fever. He was diagnosed with a quadriceps strain and discharged. The next morning the patient still had knee pain and sought treatment from an FP, who diagnosed a sprained knee. At this visit, the patient’s temperature was normal. Three days later, the patient went to another ED with a high fever and knee pain so severe that he couldn’t walk. Blood culture revealed methicillin-resistant Staphylococcus aureus (MRSA) in the knee, which quickly spread. The patient was hospitalized and required 17 surgeries.

PLAINTIFF’S CLAIM The FP should have ordered blood work and recognized the signs of infection. MRSA had been present at least 4 days before it was diagnosed.

THE DEFENSE The patient did not have a diagnosable infection the day the physician saw him and his condition had progressed over the following 3 days.

VERDICT $2.1 million Illinois verdict.

COMMENT This case reminds me of the necessity of obtaining a history of the mechanism of injury for joint pain. Absence of a definite cause should have led to a wider differential diagnosis.

Impending stroke chalked up to carpal tunnel syndrome

A WOMAN WENT TO HER PHYSICIAN COMPLAINING OF DIZZINESS, blurred vision, numbness, tingling in her hands and feet, and other symptoms. The physician diagnosed carpal tunnel syndrome. The patient visited her physician a second time, and a day later, suffered a stroke and died.


PLAINTIFF The patient specifically asked her physician if she was having a stroke and her physician told her No.


THE DEFENSE No information about the defense is available.


VERDICT $907,486 Kansas verdict.

COMMENT Certainly carpal tunnel syndrome is not sufficient to explain all of this patient’s symptoms—especially dizziness and blurred vision—but the details on this case are limited. If the patient did in fact express concern about a possible stroke, it was incumbent upon the physician to evaluate carefully and either diagnose that condition or rule it out.

Rather than coming too late, Rx for methadone came too soon

A 34-YEAR-OLD MAN ADDICTED TO OXYCODONE AND OTHER PAIN MEDICATIONS as the result of a work-related injury 10 years earlier sought treatment for his addiction from a family physician (FP) while visiting Kentucky. The patient also was abusing alprazolam. The FP administered a drug test but prescribed methadone, 180 10-mg pills, before receiving the results. The next day, the drug screen returned positive for multiple drugs, including opiates and cannabinoids. The FP’s staff tried to reach the patient, but was unsuccessful. The patient was found dead a few hours later after overdosing on a combination of methadone and alprazolam. Although 64 methadone pills were missing, the patient could not have taken all of them because only a therapeutic level of methadone was found in his system.

PLAINTIFF’S CLAIM The physician should have waited to receive the results of the drug screen before prescribing methadone. Drug Enforcement Administration guidelines allow prescription of methadone for addiction only if a patient is in withdrawal and in the process of being admitted to a treatment facility. There was no proof of withdrawal symptoms.

THE DEFENSE The treatment was reasonable and compassionate. The patient was at fault for abusing narcotics.

VERDICT $204,500 Kentucky verdict.

Could a proper history have spared this patient multiple surgeries?

A 13-YEAR-OLD CAME TO THE EMERGENCY DEPARTMENT (ED) with left knee pain and fever. He was diagnosed with a quadriceps strain and discharged. The next morning the patient still had knee pain and sought treatment from an FP, who diagnosed a sprained knee. At this visit, the patient’s temperature was normal. Three days later, the patient went to another ED with a high fever and knee pain so severe that he couldn’t walk. Blood culture revealed methicillin-resistant Staphylococcus aureus (MRSA) in the knee, which quickly spread. The patient was hospitalized and required 17 surgeries.

PLAINTIFF’S CLAIM The FP should have ordered blood work and recognized the signs of infection. MRSA had been present at least 4 days before it was diagnosed.

THE DEFENSE The patient did not have a diagnosable infection the day the physician saw him and his condition had progressed over the following 3 days.

VERDICT $2.1 million Illinois verdict.

COMMENT This case reminds me of the necessity of obtaining a history of the mechanism of injury for joint pain. Absence of a definite cause should have led to a wider differential diagnosis.

A researcher in the Center

for Cell and Gene Therapy

at Baylor College of Medicine

New virus-specific T-cells (VSTs) can effectively target multiple viruses, thereby clearing and preventing infections in transplant recipients, researchers have reported in Science Translational Medicine.

VSTs have proven effective in previous studies, but they are typically costly, can take months to produce, and often target a single virus.

The new VSTs took about 10 days to produce, are more cost-effective than standard therapy, and can target up to 5 viruses, according to the researchers.

Ann Leen, PhD, of the Baylor College of Medicine in Houston, and her colleagues developed the technique to produce the VSTs, which can target Epstein-Barr virus (EBV), adenovirus (ADV), cytomegalovirus (CMV), BK virus (BKV), and human herpesvirus 6 (HHV6).

“Unlike conventional antiviral drugs, our therapy improves virus-specific T-cell immunity—the root cause of post-transplant viral infections—providing both an effective and safe strategy to treat viruses,” Dr Leen said.

“Additionally, we can readily produce both individualized products and T-cell banks for third-party use, facilitating the extension of T-cell therapy to a standard of care for transplant recipients.”

The researchers generated 48 VST cell lines by stimulating peripheral blood mononuclear cells from allogeneic donors with overlapping peptide libraries that incorporate EBV, CMV, ADV, BKV, and HHV6 antigens.

The team then tested these VSTs in 11 patients who had received allogeneic transplants to treat leukemia, lymphoma, sickle cell disease, and other hematologic and immunodeficient disorders.

Eight of the patients had up to 4 active infections with the targeted viruses. Three patients received the VSTs to prevent infection.

The VSTs produced an overall 94% virological and clinical response that was sustained long-term. Of the 3 patients who received VSTs prophylactically, all remained free of infection for more than 3 months after infusion.

There were no immediate infusion-related toxicities. One patient developed de novo graft-vs-host disease of the skin that improved with topical steroids.

Two patients who received VSTs as prophylaxis developed transplant-associated microangiopathy, but the researchers considered this to be unrelated to VST infusion.

They noted that this is the first time BKV and HHV6 reactivations have been controlled using VSTs. Dr Leen’s team had previously reported promising results with VSTs targeting EBV, CMV, and ADV.

“This study translated improved manufacturing techniques developed in Dr Leen’s laboratory to the clinic and showed that virus-specific T cells produced with the new method could target new viruses and be ready for clinical use after 10 days,” said Helen Heslop, MD, also of Baylor College of Medicine.

“These advances mean that this therapy could be available for more patients to treat viral infections and provide long-lasting protection.”

A researcher in the Center

for Cell and Gene Therapy

at Baylor College of Medicine

New virus-specific T-cells (VSTs) can effectively target multiple viruses, thereby clearing and preventing infections in transplant recipients, researchers have reported in Science Translational Medicine.

VSTs have proven effective in previous studies, but they are typically costly, can take months to produce, and often target a single virus.

The new VSTs took about 10 days to produce, are more cost-effective than standard therapy, and can target up to 5 viruses, according to the researchers.

Ann Leen, PhD, of the Baylor College of Medicine in Houston, and her colleagues developed the technique to produce the VSTs, which can target Epstein-Barr virus (EBV), adenovirus (ADV), cytomegalovirus (CMV), BK virus (BKV), and human herpesvirus 6 (HHV6).

“Unlike conventional antiviral drugs, our therapy improves virus-specific T-cell immunity—the root cause of post-transplant viral infections—providing both an effective and safe strategy to treat viruses,” Dr Leen said.

“Additionally, we can readily produce both individualized products and T-cell banks for third-party use, facilitating the extension of T-cell therapy to a standard of care for transplant recipients.”

The researchers generated 48 VST cell lines by stimulating peripheral blood mononuclear cells from allogeneic donors with overlapping peptide libraries that incorporate EBV, CMV, ADV, BKV, and HHV6 antigens.

The team then tested these VSTs in 11 patients who had received allogeneic transplants to treat leukemia, lymphoma, sickle cell disease, and other hematologic and immunodeficient disorders.

Eight of the patients had up to 4 active infections with the targeted viruses. Three patients received the VSTs to prevent infection.

The VSTs produced an overall 94% virological and clinical response that was sustained long-term. Of the 3 patients who received VSTs prophylactically, all remained free of infection for more than 3 months after infusion.

There were no immediate infusion-related toxicities. One patient developed de novo graft-vs-host disease of the skin that improved with topical steroids.

Two patients who received VSTs as prophylaxis developed transplant-associated microangiopathy, but the researchers considered this to be unrelated to VST infusion.

They noted that this is the first time BKV and HHV6 reactivations have been controlled using VSTs. Dr Leen’s team had previously reported promising results with VSTs targeting EBV, CMV, and ADV.

“This study translated improved manufacturing techniques developed in Dr Leen’s laboratory to the clinic and showed that virus-specific T cells produced with the new method could target new viruses and be ready for clinical use after 10 days,” said Helen Heslop, MD, also of Baylor College of Medicine.

“These advances mean that this therapy could be available for more patients to treat viral infections and provide long-lasting protection.”

A researcher in the Center

for Cell and Gene Therapy

at Baylor College of Medicine

New virus-specific T-cells (VSTs) can effectively target multiple viruses, thereby clearing and preventing infections in transplant recipients, researchers have reported in Science Translational Medicine.

VSTs have proven effective in previous studies, but they are typically costly, can take months to produce, and often target a single virus.

The new VSTs took about 10 days to produce, are more cost-effective than standard therapy, and can target up to 5 viruses, according to the researchers.

Ann Leen, PhD, of the Baylor College of Medicine in Houston, and her colleagues developed the technique to produce the VSTs, which can target Epstein-Barr virus (EBV), adenovirus (ADV), cytomegalovirus (CMV), BK virus (BKV), and human herpesvirus 6 (HHV6).

“Unlike conventional antiviral drugs, our therapy improves virus-specific T-cell immunity—the root cause of post-transplant viral infections—providing both an effective and safe strategy to treat viruses,” Dr Leen said.

“Additionally, we can readily produce both individualized products and T-cell banks for third-party use, facilitating the extension of T-cell therapy to a standard of care for transplant recipients.”

The researchers generated 48 VST cell lines by stimulating peripheral blood mononuclear cells from allogeneic donors with overlapping peptide libraries that incorporate EBV, CMV, ADV, BKV, and HHV6 antigens.

The team then tested these VSTs in 11 patients who had received allogeneic transplants to treat leukemia, lymphoma, sickle cell disease, and other hematologic and immunodeficient disorders.

Eight of the patients had up to 4 active infections with the targeted viruses. Three patients received the VSTs to prevent infection.

The VSTs produced an overall 94% virological and clinical response that was sustained long-term. Of the 3 patients who received VSTs prophylactically, all remained free of infection for more than 3 months after infusion.

There were no immediate infusion-related toxicities. One patient developed de novo graft-vs-host disease of the skin that improved with topical steroids.

Two patients who received VSTs as prophylaxis developed transplant-associated microangiopathy, but the researchers considered this to be unrelated to VST infusion.

They noted that this is the first time BKV and HHV6 reactivations have been controlled using VSTs. Dr Leen’s team had previously reported promising results with VSTs targeting EBV, CMV, and ADV.

“This study translated improved manufacturing techniques developed in Dr Leen’s laboratory to the clinic and showed that virus-specific T cells produced with the new method could target new viruses and be ready for clinical use after 10 days,” said Helen Heslop, MD, also of Baylor College of Medicine.

“These advances mean that this therapy could be available for more patients to treat viral infections and provide long-lasting protection.”