Posts
Today is national mesothelioma awareness day which is fitting because so few know what mesothelioma is or its impact on its victims. Mesotheliomas are rare tumors caused predominantly by exposure to asbestos. This cancer is hard to diagnose early and harder still to treat effectively but there are advances coming and multi-disciplinary care along with good palliative care can markedly improve overall treatment.
They mostly occur on the lung lining (pleura) but can occasionally develop on the heart lining (pericardium) or elsewhere. Although the latency period from exposure to diagnosis is usually very long, often 50 years or more, once symptoms occur, the disease is often aggressive and rapidly fatal. Many people were exposed to asbestos either at work or from home exposure to a worker, but only a small minority develops the disease. The type and quantity of exposure along with some genetic predisposing factors and possibly a co-carcinogen in the form of the simian virus 40 (SV 40 was found in polio vaccines in the 1950s and 1960s because the vaccines were manufactured in monkey cells that harbored the virus) are important. Once inhaled, asbestos fibers are not removed by the lung clearance mechanisms and some may make their way to the pleura where they can slowly lead to cancer development. (It should be noted that asbestos also predisposes to lung cancer and in combination with smoking the incidence of lung cancer rises substantially.)
Mesothelioma lies dormant for years and symptoms begin only when the disease has progressed substantially. Most early symptoms are very nonspecific such as chest pain or shortness of breath. The symptoms are often related to the development of a pleural effusion (fluid between the chest wall and the pleural lining of the lung), itself a sign that the disease has progressed. There are no good early diagnostic tests. Chest X-rays and CT scans are used but by the time the cancer is visible, it is often far progressed.
Unfortunately, treatment of mesothelioma is at best disappointing. Most individuals die within a short time after diagnosis. Surgery alone has a limited role because the disease has too often progressed for surgery to be useful but as noted below it is important to “debulk” the tumor before beginning drug therapy. Radiation therapy alone as well has limited value because of the spread of disease but has a role in local control. A more systemic approach is generally needed with chemotherapy but no drug or drug combination has been found to have truly major effects. That said, the combination of cisplatin and pemetrexed has been found to give an objective response in nearly 50% of patients, a doubling of the best response rates seen previously with a single drug. Responding patients live longer and have an improved quality of life despite the temporary side effects of the drugs. Other combinations are being tested continuously and there is reason to hope for further improvements. The use of genomic analyses and from that a more targeted drug approach may well be developed in the coming years. Since it has been shown that reducing the bulk of the tumor improves survival, most treatment today combines surgery to remove as much tumor as possible followed by radiation to further eradicate the tumor locally and chemotherapy for the disease beyond their reach.
An important element in care is to be treated by a multi-disciplinary team. Look for it and accept no substitutes. For example, at the University of Maryland Greenebaum Cancer Center, a patient with suspected or known mesothelioma is seen concurrently by a thoracic surgeon, a radiation oncologist, a medical oncologist and a nurse practioneer. After examining the patient and reviewing all of the laboratory and radiographic tests, the team presents their combined recommended plan of care, taking into account the patient’s preferences and family situation. It is definitely better care and I recommend that anyone with a chronic illness, not just cancer, seek out care in a team based environment, in concert with your primary care physician as the quarterback.
All patients can benefit from a good program of supportive or palliative care, begun at the time of diagnosis. Support groups, attention to pain management, assistance in finding financial and insurance assistance and psychosocial assistance to both patient and family can markedly improve the quality of life. Complementary medicine approaches can be very helpful as well such as acupuncture or relaxation exercises to help reduce the sense of breathlessness that can accompany mesothelioma progression.
In sum, mesothelioma is a disease that is difficult to diagnose early and once symptoms occur is difficult to treat effectively. Nevertheless, there is a lot of research underway looking at prevention, early diagnosis and improved methods of treatment along with maximizing supportive care. So there is real reason to be upbeat about the future. In the meantime, there are groups that offer education and support including Mesothelioma Resource Online (sponsored by a law firm) and sites such as that of the Mayo Clinic that have good overviews. And treatment centers that use the multi-disciplinary team approach can offer superior care.
Monday, September 26, 2011
Sunday, September 18, 2011
Taking 23 Drugs From 4 Different Doctors – Lousy But Expensive Care
Lack of Care Coordination of Chronic Illnesses Leads to Excess Prescriptions, Suboptimal Care and High Expenses
Henry is a 69-year-old living alone in a small town about 60 miles from the nearest metropolitan area. He has healthcare coverage via Medicare, Medigap, and Medicare Part D. He had recently been discharged from the hospital after an ICU stay for a urinary tract infection and called to ask for some advice. He was taking twenty-three -- yes, 23 -- different prescription drugs; some once, some twice and some three times per day along with one by shot monthly. He was not certain why many of them had been prescribed and stated that despite them he did not feel well. Here is a partial list: two for heart failure (he did not know that he had heart failure!,) two for diabetes, three for high blood pressure, one to lower his cholesterol, a monthly shot of testosterone for impotence, one to shrink his prostate and one for depression.
I asked him who his primary care physician was and learned that he did not have one but rather went to four different doctors, each of whom treated different issues and none of whom shared all of his information and none of whom used electronic medial records. Whenever one of them checked his blood pressure, it would be elevated, so that doctor would either add a drug or increase the dosage. He told me that when he went to the local drug store and checked his blood pressure, it was always normal.
Henry’s story represents much of what is not working in the delivery of medical care today. He has four complex, chronic illnesses – heart failure, diabetes, hypertension and depression. These all require careful attention and care coordination, preferably by a single primary care physician who knows the patient’s home and social setting as well as his direct medical issues. The blood pressure medication story is representative. He was getting many too many drugs that he did not need and had become impotent as a result. Rather than looking for the cause, one of the doctors had given another drug [testosterone] that probably had no value but was likely enlarging his prostate. As a result he had developed an infection that had almost killed him. And all these drugs were expensive, both to him and to his Medicare Part D insurance plan.
Heart failure and diabetes together consume more than 50% of our healthcare dollars and here is a person whose care is not being adequately monitored; rather he is getting one drug after another without attention to what else is going on. This lack of care coordination is a prime reason why the costs are so high yet quality so low.
My first suggestion was that Henry needed a primary care physician, one to call his own. He found one who had just started his practice, had the time and inclination to coordinate his care and had installed an electronic medical record system. A few months later Henry called and told me that he was now taking just seven medicines and felt much better!
Henry still has four serious chronic conditions. But with a single physician serving as orchestrator rather than just intervener, one who uses an electronic medical record and who actually pays attention to Henry’s medical plus social and home life, Henry has better quality medical care, he has a much higher quality of life, he is spending less of his money and much less of Medicare, Medigap and Medicare Part D’s money. In short good care coordination is a win-win for all concerned.
And yet, care coordination is not appreciated for its importance by most physicians, insurers nor patients. Why is that?
Henry is a 69-year-old living alone in a small town about 60 miles from the nearest metropolitan area. He has healthcare coverage via Medicare, Medigap, and Medicare Part D. He had recently been discharged from the hospital after an ICU stay for a urinary tract infection and called to ask for some advice. He was taking twenty-three -- yes, 23 -- different prescription drugs; some once, some twice and some three times per day along with one by shot monthly. He was not certain why many of them had been prescribed and stated that despite them he did not feel well. Here is a partial list: two for heart failure (he did not know that he had heart failure!,) two for diabetes, three for high blood pressure, one to lower his cholesterol, a monthly shot of testosterone for impotence, one to shrink his prostate and one for depression.
I asked him who his primary care physician was and learned that he did not have one but rather went to four different doctors, each of whom treated different issues and none of whom shared all of his information and none of whom used electronic medial records. Whenever one of them checked his blood pressure, it would be elevated, so that doctor would either add a drug or increase the dosage. He told me that when he went to the local drug store and checked his blood pressure, it was always normal.
Henry’s story represents much of what is not working in the delivery of medical care today. He has four complex, chronic illnesses – heart failure, diabetes, hypertension and depression. These all require careful attention and care coordination, preferably by a single primary care physician who knows the patient’s home and social setting as well as his direct medical issues. The blood pressure medication story is representative. He was getting many too many drugs that he did not need and had become impotent as a result. Rather than looking for the cause, one of the doctors had given another drug [testosterone] that probably had no value but was likely enlarging his prostate. As a result he had developed an infection that had almost killed him. And all these drugs were expensive, both to him and to his Medicare Part D insurance plan.
Heart failure and diabetes together consume more than 50% of our healthcare dollars and here is a person whose care is not being adequately monitored; rather he is getting one drug after another without attention to what else is going on. This lack of care coordination is a prime reason why the costs are so high yet quality so low.
My first suggestion was that Henry needed a primary care physician, one to call his own. He found one who had just started his practice, had the time and inclination to coordinate his care and had installed an electronic medical record system. A few months later Henry called and told me that he was now taking just seven medicines and felt much better!
Henry still has four serious chronic conditions. But with a single physician serving as orchestrator rather than just intervener, one who uses an electronic medical record and who actually pays attention to Henry’s medical plus social and home life, Henry has better quality medical care, he has a much higher quality of life, he is spending less of his money and much less of Medicare, Medigap and Medicare Part D’s money. In short good care coordination is a win-win for all concerned.
And yet, care coordination is not appreciated for its importance by most physicians, insurers nor patients. Why is that?
Thursday, September 8, 2011
Complex, Chronic Illnesses Last a Lifetime and Consume 70% of the Healthcare Dollar
Medical care is organized to treat acute conditions but the need today is to prevent, diagnose and treat chronic illnesses. Unfortunately, we are sorely lacking in a good chronic care management system. this will be the first in a series of six posts on this issue.
Our medical care system has developed over decades and even centuries around diagnosing and treating acute illnesses such as pneumonia, a gall bladder attack or appendicitis. The internist gives an antibiotic for the pneumonia and the patient gets better. The surgeon cuts out the gall bladder or the appendix and the patient is cured. One patient; one doctor. But as the population ages, more and more individuals are developing what I will call complex, chronic diseases like heart failure, diabetes, chronic lung disease or cancer. These are diseases that once developed usually remain with the individual for life. These patients with chronic illnesses need a different approach to care. They need long term care, not episodic care. They need a multi-disciplinary, team-based approach where one physician serves as the orchestrater or quarterback and manages the myriad physician specialists and the other caregivers along with all of the tests and procedures to allow for a unified, coordinated care management approach. Not only are these diseases likely to last a lifetime, they are difficult to manage, have an adverse impact of both quality of life and mortality, and they are usually quite expensive to treat. Today 70% of our medical care expenditures go toward their treatment. As I will describe in detail later, it will take a new approach to organizing the care of these patients to both improve care and reduce the costs and this will require high quality health information technology.
However, it is valuable to first understand the implications of chronic disease. Most of us are just not aware that their incidence is rising - and rapidly. The Milken Institute (http://bit.ly/lGHFqP ) quantified some of these issues in a research report a few years ago. They evaluated cancer, diabetes [presumably type 2], hypertension, stroke, heart disease, pulmonary conditions and mental disorders. Here are some of the key findings:
• “More than 109 million Americans report having at least one of the seven diseases, for a total of 162 million cases.
• The total impact of these diseases on the economy is $1.3 trillion annually.
• Of this amount, lost productivity totals $1.1 trillion per year, while another $277 billion is spent annually on treatment.
• On our current path, in 2023 we project a 42 percent increase in cases of the seven chronic diseases.
• $4.2 trillion in treatment costs and lost economic output.
• Under a more optimistic scenario, assuming modest improvements in preventing and treating disease, we find that in 2023 we could avoid 40 million cases of chronic disease.
• We could reduce the economic impact of disease by 27 percent, or $1.1 trillion annually; we could increase the nation's GDP by $905 billion linked to productivity gains; we could also decrease treatment costs by $218 billion per year.
• Lower obesity rates alone could produce productivity gains of $254 billion and avoid $60 billion in treatment expenditures per year.”
To me the most telling and important finding is that “each has been linked to behavioral and/or environmental risk factors that broad-based prevention programs could address.” Restated, we as individuals need to take responsibility for our own health. Not every chronic illness is preventable, but most are. It is up to us to eat a nutritious diet in moderation, exercise our bodies, seek ways to reduce chronic stress and avoid tobacco. These four steps will make a huge difference in our health and our lives. Adding in dental hygiene, avoiding sexually transmitted diseases, using seat belts and not drinking and driving will further prevent many illnesses. Many do not appreciate either that following a more appropriate lifestyle will actually slow the normal aging process that ultimately leads to many of these chronic illnesses.
Meanwhile, when chronic illness does strike, it is imperative to have a single care provider take responsibility for care coordination. Someone to not only recommend tests, procedures, images and specialist visits but who will actively ensure that each provider is properly attuned to the patient’s needs and that all of the information is collected and aggregated in a meaningful manner. When this is done the quality of care rises markedly, many fewer adverse events occur, the patient is more satisfied and the costs of care are dramatically reduced. In most cases, a primary care physician is the appropriate one to coordinate care although sometimes a specialist is better equipped for this role (e.g., a very complex cancer treatment plan). To be effective, the PCP or specialist needs to have not only the willingness and interest but also the time available to actually do the care coordination – time that is not available for most PCPs today. This coupled with limited digitized health information leads to today’s inadequate care of many individuals with chronic illnesses. In future posts I will describe today’s problems with lack of care coordination and how it can be corrected.
I wonder what others think abut why the problem of chronic illnesses and the need for care coordination is just not well recognized?
Our medical care system has developed over decades and even centuries around diagnosing and treating acute illnesses such as pneumonia, a gall bladder attack or appendicitis. The internist gives an antibiotic for the pneumonia and the patient gets better. The surgeon cuts out the gall bladder or the appendix and the patient is cured. One patient; one doctor. But as the population ages, more and more individuals are developing what I will call complex, chronic diseases like heart failure, diabetes, chronic lung disease or cancer. These are diseases that once developed usually remain with the individual for life. These patients with chronic illnesses need a different approach to care. They need long term care, not episodic care. They need a multi-disciplinary, team-based approach where one physician serves as the orchestrater or quarterback and manages the myriad physician specialists and the other caregivers along with all of the tests and procedures to allow for a unified, coordinated care management approach. Not only are these diseases likely to last a lifetime, they are difficult to manage, have an adverse impact of both quality of life and mortality, and they are usually quite expensive to treat. Today 70% of our medical care expenditures go toward their treatment. As I will describe in detail later, it will take a new approach to organizing the care of these patients to both improve care and reduce the costs and this will require high quality health information technology.
However, it is valuable to first understand the implications of chronic disease. Most of us are just not aware that their incidence is rising - and rapidly. The Milken Institute (http://bit.ly/lGHFqP ) quantified some of these issues in a research report a few years ago. They evaluated cancer, diabetes [presumably type 2], hypertension, stroke, heart disease, pulmonary conditions and mental disorders. Here are some of the key findings:
• “More than 109 million Americans report having at least one of the seven diseases, for a total of 162 million cases.
• The total impact of these diseases on the economy is $1.3 trillion annually.
• Of this amount, lost productivity totals $1.1 trillion per year, while another $277 billion is spent annually on treatment.
• On our current path, in 2023 we project a 42 percent increase in cases of the seven chronic diseases.
• $4.2 trillion in treatment costs and lost economic output.
• Under a more optimistic scenario, assuming modest improvements in preventing and treating disease, we find that in 2023 we could avoid 40 million cases of chronic disease.
• We could reduce the economic impact of disease by 27 percent, or $1.1 trillion annually; we could increase the nation's GDP by $905 billion linked to productivity gains; we could also decrease treatment costs by $218 billion per year.
• Lower obesity rates alone could produce productivity gains of $254 billion and avoid $60 billion in treatment expenditures per year.”
To me the most telling and important finding is that “each has been linked to behavioral and/or environmental risk factors that broad-based prevention programs could address.” Restated, we as individuals need to take responsibility for our own health. Not every chronic illness is preventable, but most are. It is up to us to eat a nutritious diet in moderation, exercise our bodies, seek ways to reduce chronic stress and avoid tobacco. These four steps will make a huge difference in our health and our lives. Adding in dental hygiene, avoiding sexually transmitted diseases, using seat belts and not drinking and driving will further prevent many illnesses. Many do not appreciate either that following a more appropriate lifestyle will actually slow the normal aging process that ultimately leads to many of these chronic illnesses.
Meanwhile, when chronic illness does strike, it is imperative to have a single care provider take responsibility for care coordination. Someone to not only recommend tests, procedures, images and specialist visits but who will actively ensure that each provider is properly attuned to the patient’s needs and that all of the information is collected and aggregated in a meaningful manner. When this is done the quality of care rises markedly, many fewer adverse events occur, the patient is more satisfied and the costs of care are dramatically reduced. In most cases, a primary care physician is the appropriate one to coordinate care although sometimes a specialist is better equipped for this role (e.g., a very complex cancer treatment plan). To be effective, the PCP or specialist needs to have not only the willingness and interest but also the time available to actually do the care coordination – time that is not available for most PCPs today. This coupled with limited digitized health information leads to today’s inadequate care of many individuals with chronic illnesses. In future posts I will describe today’s problems with lack of care coordination and how it can be corrected.
I wonder what others think abut why the problem of chronic illnesses and the need for care coordination is just not well recognized?
Saturday, July 23, 2011
Your Lifestyle Can Prevent Sudden Cardiac Death
Adhering to a moderate yet healthy lifestyle can reduce the risk of sudden cardiac death by about 90% according to a new study. It is well known that high blood pressure, high cholesterol, and diabetes correlate with coronary artery disease. Life style factors do as well – a combination of a Mediterranean style diet, moderate regular exercise, appropriate weight and non smoking all correlate with less coronary artery disease, less stroke, less high blood pressure, less diabetes, less cancer and multiple other chronic conditions and lower (or later) mortality overall.
These same factors have now been demonstrated to also reduce risk for sudden cardiac death, i.e., a sudden arrhythmia that leads to death in less than an hour from symptom onset.
S. E. Chiuve, etal of Harvard and the Brigham and Women’s Hospital in Boston (JAMA, July 6, 2011, p62) evaluated sudden cardiac death (SCD) among 82,000 participants in the Nurses Health Study between 1984 and 2010. 321 individuals had SCD during those 26 years at an average age of 72.
The authors set out four criteria for low risk lifestyles: not smoking, BMI <25, exercise >30 minutes per day and being in the top 40th percentile of the alternate Mediterranean diet score. In essence, the latter is a diet rich in fresh vegetables and fruits, nuts, whole grains, legumes and fish with moderate intake of alcohol.
The results were clear. The more risk factors, the greater the rate of SCD. Stated differently, “a low risk life style (not smoking, exercising regularly, having a prudent diet and maintaining a healthy weight) was linearly and inversely associated with risk of SCD among women.” Those women who had all four low risk lifestyle attributes experienced a 92% lower risk of SCD compared to those who had no low risk attributes. This suggests that the vast majority of SCD could be prevented by life style modifications.
The study authors point out that although 80% of women do not smoke today, adherence to the other three factors is low. Less than 40% of middle aged women have a BMI <25, 25% drink light to moderate alcohol and only 22% exercise regularly. And although the data on diet habits is limited, a simple observation of what is purchased in the supermarket is telling.
It is evident from this study – and many others – that managing lifestyle factors can prevent serious chronic illnesses including coronary artery disease, cancer, stroke, high blood pressure and diabetes along with sudden cardiac death. This is true even for those with a genetic predisposition – “your genes need not direct your fate.”
These same factors have now been demonstrated to also reduce risk for sudden cardiac death, i.e., a sudden arrhythmia that leads to death in less than an hour from symptom onset.
S. E. Chiuve, etal of Harvard and the Brigham and Women’s Hospital in Boston (JAMA, July 6, 2011, p62) evaluated sudden cardiac death (SCD) among 82,000 participants in the Nurses Health Study between 1984 and 2010. 321 individuals had SCD during those 26 years at an average age of 72.
The authors set out four criteria for low risk lifestyles: not smoking, BMI <25, exercise >30 minutes per day and being in the top 40th percentile of the alternate Mediterranean diet score. In essence, the latter is a diet rich in fresh vegetables and fruits, nuts, whole grains, legumes and fish with moderate intake of alcohol.
The results were clear. The more risk factors, the greater the rate of SCD. Stated differently, “a low risk life style (not smoking, exercising regularly, having a prudent diet and maintaining a healthy weight) was linearly and inversely associated with risk of SCD among women.” Those women who had all four low risk lifestyle attributes experienced a 92% lower risk of SCD compared to those who had no low risk attributes. This suggests that the vast majority of SCD could be prevented by life style modifications.
The study authors point out that although 80% of women do not smoke today, adherence to the other three factors is low. Less than 40% of middle aged women have a BMI <25, 25% drink light to moderate alcohol and only 22% exercise regularly. And although the data on diet habits is limited, a simple observation of what is purchased in the supermarket is telling.
It is evident from this study – and many others – that managing lifestyle factors can prevent serious chronic illnesses including coronary artery disease, cancer, stroke, high blood pressure and diabetes along with sudden cardiac death. This is true even for those with a genetic predisposition – “your genes need not direct your fate.”
Wednesday, June 29, 2011
AIDS Stages of Care – Three So Far; Will Number Four Come Soon?
It was just 30 years ago in June 1981 when the first cases of what came to be known as Acquired Immune Deficiency Syndrome (AIDS) were published by the Centers for Disease Control (CDC) in its Morbidity and Mortality Weekly Report (MMWR.) These were men who had a wasting illness and died of unusual infections, ones of the types seen mostly in “immunocompromised hosts.” These were infections with which I was very familiar in my work treating and preventing infections in aggressively treated cancer patients at a branch of the National Cancer Institute. They included pneumocystis, cyrptococcus, toxoplasma, candidia, zoster, disseminated herpes simplex and others. They tended to develop in patients who had a type of cancer that suppressed their cellular immune function as in chronic lymphocytic leukemia, lymphoma, Hodgkin’s or after bone marrow transplantation. Some of these same infections occurred in patients who received drugs to prevent rejection after kidney, heart or lung transplants. So it was immediately clear that what would become known as AIDS was a disease that markedly affected the cellular immune function of these patients.
It would be only a few years, 1984, until the causative agent was discovered to be a retrovirus (Dr Robert Gallo and Dr Luc Montaginer) and a test was developed (Gallo) to render the blood supply safe. Meanwhile the initial years of what soon was recognized to be an epidemic were spent treating these opportunistic infections in these patients with a rapidly fatal disease once it was diagnosed as AIDS. In retrospect this was the first stage or phase of disease management; it would evolve over the years.
By 1987 the first of the antiviral drugs zidovudine (or AZT) to actually treat the underlying HIV infection was approved by the FDA after studies began at Burroughs Welcome by David Barry, MD and others and at the National Cancer Institute by Samuel Broder, MD and others. Approval came within 25 months of initial studies; a record at the time. Soon came many other drugs and by 1996 there were multiple active agents which when combined produced HAART or Highly Active Anti Retroviral Therapy. This was a distinct turning point because for the first time this lethal disease became a controllable chronic illness where one could survive for decades or possibly more. But if one stopped the drugs once immune function returned toward normal, the disease rapidly recurred in force. So it was suppressed but definitely not cured. Now the key was to get the drugs to the patient, get good compliance and give careful follow-up. Getting the drugs to the patient is no mean feat since they are inherently expensive and many patients are uninsured or underinsured. Taking multiple drugs many times per day is difficult for anyone but harder still if the person is living in poverty or is homeless or is a child with perhaps drug addicted parents. And careful follow-up is difficult for all of the same reasons plus others. And of course the challenges are perhaps even more difficult in many developing countries where the stigma of AIDS is high and the logistical means of getting both the drug and the caregiver to the patient are immense, yet this is just where the vast majority of infected individuals live.
Now a third stage has evolved. With many patients living very long times, caregivers are witnessing a set of new challenges. These are the consequences of long term chronic illness and long term drug treatment. Many patients develop a unique change in body habitus with loss of fat in the face and limbs but an increase in abdominal adipose tissue deep in and around the viscera. The metabolic syndrome is frequent and it is followed by diabetes in many. And late onset cancers of many types are being increasingly recognized. Early onset coronary artery disease is another manifestation of the changing nature of this disease and its treatment. Some believe that the chronic infection leads to chronic inflammation which in turn drives the intimal development of plaque in the coronary arteries and others like the carotids. Early onset osteoporosis is also common with 50 to 67% having osteoporosis or osteopenia well before the expected age. With continued loss of bone mineral density, the risk of fracture at an earlier age with its attendant implications for loss of mobility, hospitalization and death is high.
So for the physician, the change in these evolving stages has been from spending 90% time managing infections to 90% managing the complexities of therapy, its many complications and the long term complications of the chronic infection. Today, the HIV patient on HAART needs regular evaluations for coronary artery disease, metabolic syndrome and osteopenia with life style adjustments and possibly further drug interventions as preventive measures.
There are over 25 licensed antivirals for HIV infection and more are on the way. But whichever ones are used, they must be continued. Stopping has repeatedly proven to be linked to relapse and earlier death.
What will the forth stage be and when will it begin? Let us hope it is the discovery of a vaccine. Only a vaccine will ultimately drive the epidemic down and possibly even contain or eradicate it the way smallpox was or polio and measles could be. The HIV has proven to be very difficult to conquer with a vaccine. Some of the problems include that the initial infection usually goes unnoticed and then it remains latent for many years until the earliest evidence of AIDS appears. Another is the ubiquity of the virus and its ability to undergo sufficient change to escape immune detection. Once the T cell is infected, it is infected for life so a vaccine must be used before, not after, exposure. Of course, there has never been a vaccine produced before to a retrovirus so this in itself is a new hurdle with limited knowledge from former vaccine research to base today’s work upon. The vaccine must block the virus’ ability to enter the cell suggesting an antibody rather than a cellular immune-based vaccine. Dr Robert Gallo, Director of the Institute of Human Virology - believes the target must be the virus envelope – the “fingers” that attach to the T lymphocyte. He and his colleagues recently received over $24 million from the Gates Foundation and the military to further research in this direction.
With about 2,700,000 new infections per year worldwide, a vaccine cannot come too soon. But even when it does, the logistics of getting it to the world’s neediest will be fraught with difficulties. If getting susceptible children immunized against polio and measles has been difficult, HIV will be much more so.
It would be only a few years, 1984, until the causative agent was discovered to be a retrovirus (Dr Robert Gallo and Dr Luc Montaginer) and a test was developed (Gallo) to render the blood supply safe. Meanwhile the initial years of what soon was recognized to be an epidemic were spent treating these opportunistic infections in these patients with a rapidly fatal disease once it was diagnosed as AIDS. In retrospect this was the first stage or phase of disease management; it would evolve over the years.
By 1987 the first of the antiviral drugs zidovudine (or AZT) to actually treat the underlying HIV infection was approved by the FDA after studies began at Burroughs Welcome by David Barry, MD and others and at the National Cancer Institute by Samuel Broder, MD and others. Approval came within 25 months of initial studies; a record at the time. Soon came many other drugs and by 1996 there were multiple active agents which when combined produced HAART or Highly Active Anti Retroviral Therapy. This was a distinct turning point because for the first time this lethal disease became a controllable chronic illness where one could survive for decades or possibly more. But if one stopped the drugs once immune function returned toward normal, the disease rapidly recurred in force. So it was suppressed but definitely not cured. Now the key was to get the drugs to the patient, get good compliance and give careful follow-up. Getting the drugs to the patient is no mean feat since they are inherently expensive and many patients are uninsured or underinsured. Taking multiple drugs many times per day is difficult for anyone but harder still if the person is living in poverty or is homeless or is a child with perhaps drug addicted parents. And careful follow-up is difficult for all of the same reasons plus others. And of course the challenges are perhaps even more difficult in many developing countries where the stigma of AIDS is high and the logistical means of getting both the drug and the caregiver to the patient are immense, yet this is just where the vast majority of infected individuals live.
Now a third stage has evolved. With many patients living very long times, caregivers are witnessing a set of new challenges. These are the consequences of long term chronic illness and long term drug treatment. Many patients develop a unique change in body habitus with loss of fat in the face and limbs but an increase in abdominal adipose tissue deep in and around the viscera. The metabolic syndrome is frequent and it is followed by diabetes in many. And late onset cancers of many types are being increasingly recognized. Early onset coronary artery disease is another manifestation of the changing nature of this disease and its treatment. Some believe that the chronic infection leads to chronic inflammation which in turn drives the intimal development of plaque in the coronary arteries and others like the carotids. Early onset osteoporosis is also common with 50 to 67% having osteoporosis or osteopenia well before the expected age. With continued loss of bone mineral density, the risk of fracture at an earlier age with its attendant implications for loss of mobility, hospitalization and death is high.
So for the physician, the change in these evolving stages has been from spending 90% time managing infections to 90% managing the complexities of therapy, its many complications and the long term complications of the chronic infection. Today, the HIV patient on HAART needs regular evaluations for coronary artery disease, metabolic syndrome and osteopenia with life style adjustments and possibly further drug interventions as preventive measures.
There are over 25 licensed antivirals for HIV infection and more are on the way. But whichever ones are used, they must be continued. Stopping has repeatedly proven to be linked to relapse and earlier death.
What will the forth stage be and when will it begin? Let us hope it is the discovery of a vaccine. Only a vaccine will ultimately drive the epidemic down and possibly even contain or eradicate it the way smallpox was or polio and measles could be. The HIV has proven to be very difficult to conquer with a vaccine. Some of the problems include that the initial infection usually goes unnoticed and then it remains latent for many years until the earliest evidence of AIDS appears. Another is the ubiquity of the virus and its ability to undergo sufficient change to escape immune detection. Once the T cell is infected, it is infected for life so a vaccine must be used before, not after, exposure. Of course, there has never been a vaccine produced before to a retrovirus so this in itself is a new hurdle with limited knowledge from former vaccine research to base today’s work upon. The vaccine must block the virus’ ability to enter the cell suggesting an antibody rather than a cellular immune-based vaccine. Dr Robert Gallo, Director of the Institute of Human Virology - believes the target must be the virus envelope – the “fingers” that attach to the T lymphocyte. He and his colleagues recently received over $24 million from the Gates Foundation and the military to further research in this direction.
With about 2,700,000 new infections per year worldwide, a vaccine cannot come too soon. But even when it does, the logistics of getting it to the world’s neediest will be fraught with difficulties. If getting susceptible children immunized against polio and measles has been difficult, HIV will be much more so.
Wednesday, June 8, 2011
Improving Cancer Patient Care While Markedly Reducing Costs
It is often difficult to appreciate that improving the care of patients can actually reduce the costs of care. Last year Dr H Brody wrote in the New England Journal of Medicine (vol 362, p283-5) about “Medicine’s ethical responsibility for health care reform – the top five list.” In essence he challenged physicians to be first to find ways to rationally reduce health care costs by identifying the top five tests or treatments in any given specialty or subspecialty that could be markedly reduced or even eliminated without harm to the patient. He made some specific suggestions to get things started.
Now Drs.Thomas Smith and Bruce Hillner, two oncologists from the Massey Cancer Center in Virginia, have accepted the challenge and published in the same journal (vol 364, p21, May 26, 2011) a proposed list of five suggested changes in medical oncologist’s behaviors and five changes in attitudes and practices. Their proposal is noteworthy because it directly addresses some of the most important issues that affect cancer patient care yet inordinately increases the cost of that care.
I will not repeat each of their suggestions but will comment on a few. One change in behavior is to limit chemotherapy to patients with a good performance status (with an exception for those with highly responsive disease.) It is well known that a person’s performance status is a very strong predictor of whether a patient will respond to a treatment or have any meaningful extension of survival. The authors point out that their proposal is in line with current guidelines by national oncology organizations. They make the simple recommendation that a patient should not be given chemotherapy if he or she cannot walk into the clinic unaided. Unfortunately, many oncologists today push ahead with further treatment despite their patient’s performance status.
Another suggestion is to “replace the routine use of white blood cell stimulating factors with a reduction in chemotherapy dose in metastatic solid tumors.” The hematopoietic colony stimulating factors (CSFs) are very valuable in pushing the bone marrow to recover white blood cell numbers after aggressive treatments. The concept is that infection is common when the white blood cell count drops below 500 per ul. This is a common occurrence in the treatment of acute leukemia and some other situations where very aggressive chemotherapy is used and the CSFs can be lifesaving in those patients. But they are not needed for modest reductions in WBC counts. In truth, drops below 500/ul rarely happen in the treatment of patients with most solid tumors such as breast, prostate, lung or colon cancer. Yet these very expensive stimulants are used routinely but at high cost. Smith and Hillner suggest that at about $3500 per injection, the sales by oncologists to their patients’ amount to some $1.25 billion per year.
And there is the rub – to change these two practice patterns would be to substantially reduce the oncologist’s income. Oncologists earn a decent but not high income from basic care of their patients. But fully another one half comes from the administration of chemotherapy and support medications such as drugs for nausea and vomiting and drugs to boost the bone marrow to produce red blood cells (erythropoietin) and white blood cells ( pegfilgrastim, Neulasta). In effect they serve as a pharmacy for these drugs, buying them wholesale from distributors, preparing them and administering them while collecting a markup for their effort. This brings their incomes to among the highest among internists. To cut back on chemotherapy or Neulasta administration would have a telling financial impact.
Another suggestion, this one a change in attitude, is to address the importance of end-of-life discussions. The authors point out the truism that such discussions are a critical perquisite to good care planning by both doctor and patient and family. But they point out that far too often, oncologists wait until new symptoms appear or until they feel there is nothing else that can be done before entering this type of discussion. But when such discussions are held at an appropriate time, there is greater use of hospice and “less depression or anxiety, less aggressive end-of-life care and [patients] rarely die in an intensive care unit or on a ventilator.” Further “it allows the surviving caregiver to have a better quality of life and would save our society millions of dollars.” And yet, such discussions are all too infrequent or come too late. It is the physicians’ obligation to their patients and patients’ families to be honest and direct, albeit caring and compassionate at the same time.
With these changes (and some of the others that Smith and Hillner recommend) in behaviors and attitudes, the care of cancer patients would be greatly improved yet the costs would be very greatly reduced. That is a good exchange. Let’s hope these suggestions become the norm of care and that physicians in other specialties take up Brody’s challenge as effectively.
Now Drs.Thomas Smith and Bruce Hillner, two oncologists from the Massey Cancer Center in Virginia, have accepted the challenge and published in the same journal (vol 364, p21, May 26, 2011) a proposed list of five suggested changes in medical oncologist’s behaviors and five changes in attitudes and practices. Their proposal is noteworthy because it directly addresses some of the most important issues that affect cancer patient care yet inordinately increases the cost of that care.
I will not repeat each of their suggestions but will comment on a few. One change in behavior is to limit chemotherapy to patients with a good performance status (with an exception for those with highly responsive disease.) It is well known that a person’s performance status is a very strong predictor of whether a patient will respond to a treatment or have any meaningful extension of survival. The authors point out that their proposal is in line with current guidelines by national oncology organizations. They make the simple recommendation that a patient should not be given chemotherapy if he or she cannot walk into the clinic unaided. Unfortunately, many oncologists today push ahead with further treatment despite their patient’s performance status.
Another suggestion is to “replace the routine use of white blood cell stimulating factors with a reduction in chemotherapy dose in metastatic solid tumors.” The hematopoietic colony stimulating factors (CSFs) are very valuable in pushing the bone marrow to recover white blood cell numbers after aggressive treatments. The concept is that infection is common when the white blood cell count drops below 500 per ul. This is a common occurrence in the treatment of acute leukemia and some other situations where very aggressive chemotherapy is used and the CSFs can be lifesaving in those patients. But they are not needed for modest reductions in WBC counts. In truth, drops below 500/ul rarely happen in the treatment of patients with most solid tumors such as breast, prostate, lung or colon cancer. Yet these very expensive stimulants are used routinely but at high cost. Smith and Hillner suggest that at about $3500 per injection, the sales by oncologists to their patients’ amount to some $1.25 billion per year.
And there is the rub – to change these two practice patterns would be to substantially reduce the oncologist’s income. Oncologists earn a decent but not high income from basic care of their patients. But fully another one half comes from the administration of chemotherapy and support medications such as drugs for nausea and vomiting and drugs to boost the bone marrow to produce red blood cells (erythropoietin) and white blood cells ( pegfilgrastim, Neulasta). In effect they serve as a pharmacy for these drugs, buying them wholesale from distributors, preparing them and administering them while collecting a markup for their effort. This brings their incomes to among the highest among internists. To cut back on chemotherapy or Neulasta administration would have a telling financial impact.
Another suggestion, this one a change in attitude, is to address the importance of end-of-life discussions. The authors point out the truism that such discussions are a critical perquisite to good care planning by both doctor and patient and family. But they point out that far too often, oncologists wait until new symptoms appear or until they feel there is nothing else that can be done before entering this type of discussion. But when such discussions are held at an appropriate time, there is greater use of hospice and “less depression or anxiety, less aggressive end-of-life care and [patients] rarely die in an intensive care unit or on a ventilator.” Further “it allows the surviving caregiver to have a better quality of life and would save our society millions of dollars.” And yet, such discussions are all too infrequent or come too late. It is the physicians’ obligation to their patients and patients’ families to be honest and direct, albeit caring and compassionate at the same time.
With these changes (and some of the others that Smith and Hillner recommend) in behaviors and attitudes, the care of cancer patients would be greatly improved yet the costs would be very greatly reduced. That is a good exchange. Let’s hope these suggestions become the norm of care and that physicians in other specialties take up Brody’s challenge as effectively.
Friday, June 3, 2011
Using Genomics to Improve Treatment of Lung Cancer
Drug companies can use genomics to create targeted drugs like imatinib (Gleevec) and trastuzumab (Herceptin.) Physicians can then use the results of genomic studies to guide prescribing. As discussed in prior posts, a person with Philadelphia chromosome-positive (i.e., having the BCR-ABL translocation with its aberrant tyrosine kinase) chronic myelocytic leukemia will likely respond to Gleevec. And a woman whose breast cancer shows high levels of the Her2neu receptor will likely respond to Herceptin. There would be no reason to treat a Philadelphia chromosome-negative CML patient with Gleevec nor a breast cancer patient without Her2neu receptors with Herceptin.
Recently the treatment of lung cancer has advanced considerably as a result of genomic analysis of the tumor and the development of targeted drugs. Lung cancer is divided into a number of different categories based on the microscopic appearance under the microscope. One type is called small cell and the others are usually “lumped” together as “non small cell” lung cancer because the former is treated much differently than the latter group. The non small cell lung cancers can be genomically evaluated to determine if there are certain common genetic mutations such as KRAS, EGRF, MEK and other mutations or the EML4-ALK translocation.
Patients with the EML4-ALK translocation respond reasonably well to the tyrosine kinase inhibitor crizotinib (somewhat similar to the one used for CML). As with the translocation seen in CML, this is a fusion gene that occurs during a translocation of two parts of two chromosomes that lead to a portion of the normal EML4 gene being fused next to the normal ALK tyrosine kinase gene. When this happens the new gene transcribes a variant tyrosine kinase protein which leads in part to the development or progression of lung cancer. Studies to date indicate it to occur mostly in the subtype called adenocarcinoma, in those with prior treatment, in younger patients and those who have no or a minimal smoking history. Although this represents just a small subset of all lung cancer patients, treatment of them in a Phase 1 trial with crizotinib resulted in a confirmed response in 57% (47 of 82) of patients with another 33% (27 of 82) having stabilized disease. [Kwak et al, New England Journal of Medicine, Oct 28, 2010] Although not a randomized trial, it is well known that most second line treatment regimens have no better than a 10% response rate so this would appear to be a breakthrough of sorts. Certainly it is not a panacea, nor a cure. But with minimal side effects these patients received some useful benefit and probably will have a lengthened survival Further studies will need to be done but if it is correct that about 5% of lung cancer patients have this fusion gene, then about 9000 patients per year would potentially benefit form crizotinib or similar ALK kinase inhibitors. Concurrently, one would not choose to use this drug in patients without this fusion gene and its abnormal protein. It also appeared that some patients had a further mutation such that crizotinib was not effective in them. [Note: Crizotinib is not yet approved by the FDA so access to the drug is via clinical trials.]
Patients who have the EGRF mutation appear to be distinct from those who do not as to response to the drugs erlotinib (Tarceva) and gefitinib (Iressa). EGRF is a tyrosine kinase that when mutated appears to play a role in lung cancer development and progression. Those who do have this mutated gene and its transcribed protein will respond to these two drugs in about 70% of cases with progression free survival of about a year and total survival of about two years. This would appear to be superior to standard drug therapy used today. Without this mutation, the patient will do much better treated with chemotherapy. So the treatment of a new patient with lung cancer today should include genomic analysis of the tumor so that the patient can receive the most appropriate first line treatment and then reanalysis later to determine if there are further mutations or translocation that would direct second line treatment options.
This is just one more example of how genomics is making medical care more custom-tailored, one of the five key medical megatrends.
Recently the treatment of lung cancer has advanced considerably as a result of genomic analysis of the tumor and the development of targeted drugs. Lung cancer is divided into a number of different categories based on the microscopic appearance under the microscope. One type is called small cell and the others are usually “lumped” together as “non small cell” lung cancer because the former is treated much differently than the latter group. The non small cell lung cancers can be genomically evaluated to determine if there are certain common genetic mutations such as KRAS, EGRF, MEK and other mutations or the EML4-ALK translocation.
Patients with the EML4-ALK translocation respond reasonably well to the tyrosine kinase inhibitor crizotinib (somewhat similar to the one used for CML). As with the translocation seen in CML, this is a fusion gene that occurs during a translocation of two parts of two chromosomes that lead to a portion of the normal EML4 gene being fused next to the normal ALK tyrosine kinase gene. When this happens the new gene transcribes a variant tyrosine kinase protein which leads in part to the development or progression of lung cancer. Studies to date indicate it to occur mostly in the subtype called adenocarcinoma, in those with prior treatment, in younger patients and those who have no or a minimal smoking history. Although this represents just a small subset of all lung cancer patients, treatment of them in a Phase 1 trial with crizotinib resulted in a confirmed response in 57% (47 of 82) of patients with another 33% (27 of 82) having stabilized disease. [Kwak et al, New England Journal of Medicine, Oct 28, 2010] Although not a randomized trial, it is well known that most second line treatment regimens have no better than a 10% response rate so this would appear to be a breakthrough of sorts. Certainly it is not a panacea, nor a cure. But with minimal side effects these patients received some useful benefit and probably will have a lengthened survival Further studies will need to be done but if it is correct that about 5% of lung cancer patients have this fusion gene, then about 9000 patients per year would potentially benefit form crizotinib or similar ALK kinase inhibitors. Concurrently, one would not choose to use this drug in patients without this fusion gene and its abnormal protein. It also appeared that some patients had a further mutation such that crizotinib was not effective in them. [Note: Crizotinib is not yet approved by the FDA so access to the drug is via clinical trials.]
Patients who have the EGRF mutation appear to be distinct from those who do not as to response to the drugs erlotinib (Tarceva) and gefitinib (Iressa). EGRF is a tyrosine kinase that when mutated appears to play a role in lung cancer development and progression. Those who do have this mutated gene and its transcribed protein will respond to these two drugs in about 70% of cases with progression free survival of about a year and total survival of about two years. This would appear to be superior to standard drug therapy used today. Without this mutation, the patient will do much better treated with chemotherapy. So the treatment of a new patient with lung cancer today should include genomic analysis of the tumor so that the patient can receive the most appropriate first line treatment and then reanalysis later to determine if there are further mutations or translocation that would direct second line treatment options.
This is just one more example of how genomics is making medical care more custom-tailored, one of the five key medical megatrends.
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