What Really Needs To Be Done About the Critical Shortages of Cancer Drugs

The following is an Op Ed written by myself and colleague Dr Curt Civin and published December 7, 2011 in the Baltimore Sun.

Hospitals nationwide are experiencing shortages of critical generic intravenous drugs. We believe a fundamental reason for this national shortage is government price controls. With these limits there is little incentive to invest in new facilities and technologies, leading to equipment failures. Manufacturers have little economic incentive to prepare proactively for the quality assurance issues that routinely arise in the manufacturing of a sterile injectable compound. To reincentivize this process, the market needs to be free. spurring more manufacturers to produce these drugs, encourage reinvestment in facilities and the stockpiling of reserves.
The drugs in shortest supply include those used in critical care units such as norepinephrine for shock, antibiotics for infections, and cancer chemotherapy. Almost all are generics and manufactured by a just few companies. Among the oncology drugs in short supply are cytarabine and leukovorin. Cytarabine is the best single drug for acute myeloid leukemia. Leukovorin is used in childhood acute lymphoblastic leukemia. These are older “off patent” drugs. As generics, they are far less expensive that newer drugs. They have stood the test of time, are still used extensively and are necessary for optimal patient care. Individual patients need exactly the right drugs on precisely the right schedule – no substitutes; now, not later. As pointed out in Congressional testimony and a Wall Street Journal editorial, these shortages are having a major negative impact for ongoing clinical trials designed to improve cancer treatment results.
Another critically needed cancer drug is Doxil, a drug used for the treatment of many cancers. It is sold by Johnson and Johnson (J&J) and until recently it had been manufactured on contract for J&J by Ben Venue Laboratories. Unfortunately, Ben Venue is exiting the contract drug business. Thus, Doxil is not currently available.
Prior to 2003, Medicare paid for cancer chemotherapy injectables based on the average wholesale price. But with no transparency, some distributors or physicians could reap huge profits. To combat this and with the best of intentions, a new system was developed as part of the Medicare Modernization Act of 2003, based instead on the average selling price updated quarterly. Oncologists, who purchase the drugs from distributors and then administer them, are reimbursed the ASP plus a 6% administrative fee. This would at first glace seem perfectly reasonable. Not quite. In effect, it means that Medicare allows a maximum of only a 6% increase per year; any more and the reimbursement would be less than the cost. In the generic drug business prices can decline tremendously. If the price drops too low, some manufacturers simply cease producing it and use their capacity to make other more profitable drugs. The remaining producers cannot raise their prices more than 6%, so they have little incentive to make up for lost capacity by investing in new plant or equipment. The system has broken and needs to be fixed soon or patients will die.
President Obama recently signed an executive order requiring manufacturers to notify the FDA at least six months in advance of discontinuing a critical injectable sterile medication. This will be useful in a few situations, such as Doxil, but it will be of little help when companies must suspend manufacturing immediately due to finding a contaminant, having an equipment breakdown, etc. The New York Times called the President’s measures “useful first steps,” but emphasized that Congress needs to take up long stalled legislation. We agree but believe that the legislation needs to focus on raising the profit margin allowed under Medicare. This could be done by permitting the marketplace to set the value of these critical drugs in a transparent manner.
Concurrently, oncologists should be paid an appropriate administrative fee based on the time and effort required per specific drug rather than a flat percentage of the cost. This would eliminate the temptation noted recently in the New England Journal of Medicine to substitute a more expensive drug (6% of a higher priced drug means a greater income than 6% of a lower cost drug).
With our recommendation, prices will still be very cheap compared to on patent drugs yet rise to the point sufficiently profitable for the generic producers to invest in their manufacturing capacity, create redundant production lines and encourage more manufacturers to enter the marketplace. Combined, these changes will reduce quality control issues, create backup options, and maintain a stable supply of these vital drugs for the patients who desperately need them.

Curt I Civin, MD, writing in his personal capacity, is professor of pediatrics and physiology, director of the Center for Stem Cell Biology & Regenerative Medicine, and associate dean for research at the University of Maryland School of Medicine. Stephen C Schimpff, MD is former CEO of the University of Maryland Medical Center, professor of medicine and author of “The Future of Health Care Delivery – Why It Must Change and How It Will Affect You,”  to be published in February by Potomac Books.

We Are Ruining Our Children’s Future Health

Our children (and grandchildren) are the future and we are responsible for their growth and development. As responsible parties, we are clearly failing.

That is my interpretation of the report issued a few days ago by the Centers for Disease Control (CDC) on seven criteria known to the associate with ideal cardiovascular health as part of the National Health and Nutrition Examinination Survey. They are defined, briefly, as 1) a diet with 4 ½ servings of fruits and vegetables per day, 3 servings of whole grains per day, fish twice per week, no more than 1500 mg of sodium (salt) per day, and less than 36 oz of sweetened drinks per week. Also 2) a normal body mass index (BMI) which roughly means not being overweight, 3) not smoking, 4) having at least one hour of physical activity per day, 5) a normal level of cholesterol, 6) normal blood pressure and 7) normal blood glucose (blood sugar.)

Infants start out life with a normal risk for heart disease but risk increases rapidly from preteens and into adolescence. We have known for some time that kids are getting less and less exercise, even less as they progress into the teenage years.

But this new report is striking. Not one child out of 4157 aged 12 to 17 in the study group monitored between 2003 and 2008 was in the “ideal” category for diet. And only 16% of the boys and 11% of the girls were in the ideal range for all of the remaining six categories.

Looked at differently, 20% were obese (not just overweight); about 20% smoked; about 50% had too little physical activity; cholesterol was elevated in about 30%; and glucose was somewhat high in about 40%. One bright spot – blood pressure was elevated in less than 10%.

This report is important for at least two reasons. We know that atherosclerosis begins to build up in childhood and young adults even though angina and heart attacks are not common until a few decades later. It is essential to maintain a healthy lifestyle and this needs to begin in childhood. Second, we know that the 7 criteria are each associated with a lessening of heart disease risk when kept to the normal or ideal level (diet, weight, not smoking, etc) and that each, when not meeting the standards, add together to increase the risk of cardiovascular disease in later life.

These are not impossible standards to meet. Diet might be most difficult, especially for kids in urban or rural poor areas who have less access to fresh fruits and veggies but there is little excuse for over indulging in salt and sodas. One big problem is the ready availability of processed foods – foods high in salt, fat and sugars including high fructose corn syrup – along with ubiquitous sodas, often in very large containers.

Parents – they are your children. They need good food, they need lots of activity, and they need parental support to avoid tobacco and processed foods. They are your (and all of our) future.

Frailty – Common In Older Ages But Is It Preventable?

Americans are aging – fast. And that means more chronic illnesses like arthritis, heart failure and cancer. It also means more falls, more osteoporotic fractures, poorer hearing and vision and myriad other problems we equate with aging. It also means some older folks become “frail,” irrespective of chronologic age.

You know a person is frail when you see him or her – instinctively you will think a person is “frail” if they are “skinny,” weak, tired, inactive and slow. But frailty can actually be measured. Among the systems is one developed by the Cardiovascular Health Study, a longitudinal program that evaluated cardiovascular risk factors with annual examinations from 1989 to 1999 for individuals over age 65. This was followed through to the present with annual telephone follow-ups. Their “frailty indicator variables” include unintentional weight loss of more than ten pounds (as some measure of loss of muscle mass), grip strength,(as a measure of weakness) , fatigue score on a standardized test (as a measure of tired), physical activity (measure of inactivity), and walking speed (“slowness.”)

Using this approach, and if we define “frail” as having three or more of these five characteristics, about 7% of adults over age 65 living in the community will be regarded as frail. Importantly, frailty is not the result of co-morbidities but co-morbidity is a risk factor for frailty and disability is a frequent outcome of frailty.

With this definition of 3 or more characteristics, frail individuals will be found to have more falls, more hospitalizations, more fractures, increased sleep disordered breathing and more difficulty with the activities of daily living. They also, on average, demonstrate certain biological differences such as elevated C-reactive protein.

One person – otherwise healthy – might become frail in his 70’s whereas someone else might not until his 90’s or even after 100. That would suggest a possible genetic component and some preliminary studies as consistent with this theory.

We know that our bodies begin to “decline” with aging beginning in middle age. Bone mineral density for example declines about 1% per year. So too does cardiac function, muscle mass, lung capacity, etc. These processes are “normal” but can be slowed. Regular aerobic and weight bearing exercise will help maintain all of these functions. The decline will continue but at a slower rate.

What can we each do now? After checking in with your health care provider, a reasonable regimen might include:

Daily aerobic exercise for about 30 minutes
Resistance exercises (weights, Nautilus, etc)
Balance training

A personal trainer or physical therapist might be useful to give guidance and check out if the exercises are being done correctly and with enough intensity.

Then it might be good to add in a

Nutrition consultation to be sure your diet is appropriate for your age and lifestyle. For example, do you get enough protein in your diet?

And you might want to include some mental exercises to complement your physical ones. Studying a foreign language, playing chess or bridge, or Sudoku challenges your brain – but not TV watching or mindless books (even if they are interesting.)

This approach will slow the normal aging process and it may even help prevent the onset of frailty and is sequela. And for certain you will feel better, have fewer falls and other problems common with older age.

Reasonable Goals for Health Insurance Coverage and Defining Medical Necessity

Health care should be a right but it needs to be paired with some responsibility – some share of the cost, especially for routine care, and some attention to maintaining a reasonably healthy life style. To do so will not only lead to better health but reduced expenses overall – positive outcomes for all.
One of the major goals of the Affordable Care Act is to reduce the number of uninsured from the current about 50 million people (or 16+% of the US population) by both offering Medicaid to many more individuals and creating state-based insurance exchanges for individuals who cannot obtain insurance at their worksite. Medicaid will be available for those at <133% of the federal poverty rate (currently $22,050). The insurance exchanges will be available to everyone but those with income below 400% of the poverty level ($88,200 for a family of four) will be eligible for tax credits based on actual income. Unlike Medicaid which has essentially no cost sharing by the individual, insurance from the exchanges will be purchased at one of four levels – 60, 70, 80 or 90% of the approved covered expenses will be paid by the insurance; the remainder will be the individuals’ responsibility. Higher deductibles will likely correspond to lower premiums.

The Institute of Medicine (IOM), at the request of the Department of Health and Human Services, formed a committee to consider the process for defining “essential health benefits” which ultimately will translate into what is covered or not by the insurance from the exchanges. The IOM, wisely in my opinion, emphasized he need for affordability rather than just comprehensiveness. They argued that coverage should be “evidence-based, specific and value promoting over time.” They proposed that medical necessity should be based upon clinical appropriateness, best scientific evidence and a likelihood of providing an “increased health benefit…that justifies an added cost.” [For a fuller discussion of the IOM recommendations, see John Iglehart’s article in the New England Journal of Medicine, Oct 20, 2011]

These seem like wise and sensible proposals. Too often there has been a “push” to insist on very comprehensive coverage, little attention to evidence-based criteria and little or not cost sharing by the patient.

My own hope is to see insurance that carries high deductibles to encourage each of us to personally monitor our health expenditures. When we have our own money at stake, we are more likely to ask our physician if that MRI, procedure or specialist visit is really needed of if it is “just to be complete.” That high deductible may also encourage us to maintain a better life style and maintain our health. That is good for us and reduces the overall costs further.

My new book discusses these topics in detail – “The Future of Health Care Delivery, Why It Must Change and How It Will Affect You” will be published in Feb, 2012 by Potomac Books

Kudos for Electronic Medication Ordering But Problems with Electronic Physician Documentation

I toured a major medical center recently to get a look at the robots in the pharmacy and to understand how the electronic medical record worked there. I was particularly interested in the new robot that made up “injectables,” the fluid bags filled with medications to be given intravenously, such as antibiotics. There was also a robot that selects pills and tablets based on bar code technology. A third robot actually delivers the medication to the individual nursing units, a little “R2D2.” The robots depend on the electronic medical record (in this case purchased from a major vendor oriented toward large hospitals and academic medical centers) for input. It begins with the physician placing an order that includes the drug name, dose, route and frequency of administration. The pharmacist reviews the order and then sends it to the appropriate robot for production. It is a terrific system that reduces errors, coaches the physician during the ordering process, and allows the pharmacist to spend more time using his or her knowledge rather than in preparation activities.

I then asked to see a physician using the electronic medical record to enter an order. The doctor showed me how it was done and how it helped her to avoid mistakes. Basically she was very complimentary of the new system.

So I then asked if she also found it effective for writing her medical documentation such as history and progress notes. Medical documentation is the essential communication tool providers use to collaborate on patient treatment. “No way,” was the immediate response. “It [Electronic Physician Documentation] is too cumbersome, takes much too much time, does not allow me to enter information in a logical manner – basically it wants me to use [the computer’s] logic, not mine. So I just hand-write my notes.” Not a good recommendation, so I asked a few more physicians at different locations and got the same response. I checked with the hospital CIO and learned that few physicians actually used the “physician documentation” part of the system although they gave high marks to the other elements such as ordering tests and reviewing results and images. Since then I have asked similar questions at multiple hospitals, using different major vendor systems, always with about the same response. Clearly, there is a problem here.

The long standing written methodology for physician documentation works sort of like this: the doctor writes an “Admission Note” which includes the patient’s history of the present illness, social and medical history, examination findings, diagnostic test findings, a presumed diagnosis, further testing to be done and a treatment plan. Concurrently, the doctor writes “Orders” such as bed rest, frequency of vital signs to be collected, type of diet and drug orders. Thereafter, the doctor enters “Progress Notes” on a daily or greater basis that summarizes the patient’s status since the last physician visit, new information, supplemental orders for additional testing and new treatment approaches. With an electronic medical record many commercial systems try to adjust this process to use “Check offs” and to eliminate or markedly reduce typing which cannot be readily manipulated for later analysis. Some details are readily done by “check offs” such as age, race, gender and even much of the examination. But the “history,” especially that of a person with one or more chronic illnesses, is by nature a narrative not readily amenable to check offs. A second issue is that the physician deals with the patient and therefore with the chart in a discontinuous manner. For example, he or she might visit each patient early in the morning, then go to radiology to review the films with the radiologist, then to pathology to look at slides with the pathologist, etc. Meanwhile the nurse calls with a problem to be resolved with a verbal order or an electronic order urgently. Each of these encounters may need an update to the medical record and so it needs to be adaptable to that requirement. In teaching hospitals, the intern and residents need a simple manner to sign out to each other with a list of problems for each patient – absent that it means taking notes at a sign out conference. Each of these are issues that most of the current commercial vendors have not resolved which is why the doctor I queried responded “No way.” This problem needs to be resolved promptly if electronic medical records are to gain their full potential.

There is hope, however, with innovative niche companies and new technologies to solve these problems where the vendor market has traditionally been unable to do so. Companies such as Salar, Inc., which have carefully observed how physicians work, have found ways to extend hospital EMR’s to deliver a more flexible templating solution. [Disclosure: I was a Salar board member for five years.] Furthermore, advances in voice recognition and natural language processing give promise of allowing physicians to continue to document in their own methods (allowing for narrative and flexible workflow) while coding the information and delivering the information to the EMR.

I believe that once good systems are in place for physician documentation, the electronic medical record will be rapidly adapted with the attendant advantages for patient, doctor, hospital and insurer. This will be especially important as we increasingly need to care for patients with multiple chronic illnesses with the multi-disciplinary team-based approach. The question at hand is why have the major vendors not corrected/improved their systems to make physician documentation easy and thorough for the doc? I suspect that it is because they have large bureaucracies with software written by those who have not actually observed how physicians work. Hopefully this will change.

My new book “The Future of Health-Care Delivery: Why It Must Change and How It Will Affect You,” from which this post is adapted, will be published Feb 28, 2012 by Potomac Books

Targeted Therapies Lead To Exciting Improvements in the Treatment of Melanoma Patients

Melanoma is the most virulent form of skin cancer with a rapidly rising incidence due to prior sun exposure. About 40,000 men and 30,000 women per year in the USA develop melanoma. In addition to sun exposure, there are independent genetic risk factors such as a variation in the “red hair” gene that increases in frequency the further one’s ancestral home is north of Africa.

Melanoma, as with all cancers, has its own genotype variations. There are at least five melanoma genotypes which can be detected with molecular profiling (for more information look at Vanderbilt’s “My cancer genome”). Each type has its own different mutations.

Just fewer than 50% of melanomas have a mutation in BRAF, a cell signaling pathway. Approximately 90% of the BRAF mutations produce a substitution of glutamic acid for valine at codon 600 in the gene product. This is apparently a critical factor in the development and aggressiveness of melanoma cells. About 20% of melanomas have an NRAS mutation, 1% have both BRAF and NRAS and 30% have neither mutation. Interestingly, among patients 20-30 years old, 86% will have the BRAF mutation but only 22% of those over 70 years have it. As a result, the new drugs that target the BRAF mutation gene product will be of relatively more utility in younger than in older individuals.
One of the new targeted drugs is an inhibitor of the BRAF mutated gene product called Vemurafenib – the name based on “V600E mutated BRAF inhibitor.” Vemurafenib (Zelboraf) decreased the relative risk of death by 63% and the risk of tumor progression by 74% when combined with dacarbazine (an alkylating agent also known as DTIC or imidazole carboxamide which has been the long time standard of care for metastatic melanoma) compared to dacarbazine alone in a large cohort of patients with the BRAF V600E mutation in their melanoma. The FDA approved this drug for treating melanoma in August, 2011 for BRAF mutation positive patients as determined with a companion diagnostic device called the BRAF V600 Mutation Test.
In this phase 3 trial of 675 patients, there as 48% response rate and a 5.3 month median progression free survival with Vemurafenib compared with dacarbazine with its 5% response rate and 1.6 month progression free survival median. Exciting as this sounds, it is no panacea and certainly not a cure although some patients had both excellent tumor shrinkage and long survivals, both rarely seen with dacarbazine. Side effects were acceptable but squamous cell skin cancers developed in some and activity declined over time. To deal with the latter, new trials are evaluating combined targeted therapy by adding a MEK gene product inhibitor. In early results, there was increased activity and fewer skin tumors developing.
The cost, according to the manufacturer, Genentech, will be about $60,000 for a course of therapy over about six months. Vemurafenib tends to have rapid responses and so might be especially important for patients with extensive disease or severe symptoms. Despite the enthusiasm for a drug that actually has real benefit, it is not curative therapy nor does it produce truly long lasting responses. Still it is a major improvement and offers real benefits and hope to patients, a testament to the concept of targeted therapy based on genomic information.
Another drug, ipilimumab (Yervoy) also has shown substantial activity against metastatic melanoma. Ipilimumab is a monoclonal antibody that binds to the cytotoxic T-lymphocyte antigen 4 (CTLA 4) and acts to enhance T-cell activation. In other words, it activates the immune system. It was approved by the FDA in March, 2011. The basic clinical trial that led to approval had 502 poor prognosis patients yet with good performance status. Patients randomized to ipilimumab plus dacarbazine had a longer time of progression free survival and the responses that developed persisted longer (19.3 vs. 8.1 months) than those who received dacarbazine alone. Overall survival was 11.2 months compared to 9.1 months but there were about 25% alive at four years which is quite noteworthy. Unfortunately, it can cause or exacerbate autoimmune disease because it allows T-cells to stay activated. The manufacturer, Bristol Meyers Squibb, at the request of the FDA, has sent a booklet to all medical oncologists to guide attention to these potentially serious side effects. It costs about $120,000 for a course of treatment.

So these are encouraging improvements for a tumor that has been exceptionally resistant to new approaches to treatment over the years. The key has been to understand the genetic mutations in the tumor, then to analyze the gene product and finally to create a drug that inhibits the gene product’s activity – genomic targeted therapy. Going forward, treatment will probably be a combination of compounds that interact with various mutations’ effects, hopefully augmenting the activity shown by these two drugs to date.

Primary Care Physicians Can Greatly Reduce The Costs Of Care, Especially For Chronic Diseases

In an earlier post I described the problem of excessive and inappropriate drug prescribing when a patient with multiple chronic illnesses did not have good care coordination by a single primary care physician. In this post I will relate the story of a lady who had an excellent primary care physician but the communication system broke down when she went elsewhere for a single visit. In her case the problem was the recommendation of an inappropriate medical technology for her chronic condition.

Ellen is an elderly lady who had been going to the same primary care physician (PCP) for over twenty years. On nearly every visit she said that she felt “tired.” Repeated history and exam revealed no cause nor did logical tests such as those for anemia or hypothyroidism. She then developed syncopal episodes – times she would black out and fall to the floor, once bruising her head when she fell against the stove, and then waking up in a few minutes. Evaluation showed that she had intermittent episodes of bradycardia, or very slow heart rate, resulting in the drop attacks. In consultation with a cardiologist, it was decided to insert a single lead pacemaker. The pacemaker senses the electrical action in the heart and when the rate drops below a set level, it immediately begins to send out an electrical stimulus – on demand - to the heart muscle so that it will contract at a normal rate. The pacemaker is expensive and the procedure to place it is expensive as well. But it worked perfectly and she no longer had the attacks that were not only scary and medically dangerous but seriously impacting her quality of life. A good return on investment.

A few months later during a visit to her daughter, she went to that daughter’s internist for an unrelated reason; he urged her to see a cardiologist colleague. Both the internist and the new cardiologist heard the usual complaint of “being tired” and assumed it related to her cardiac status. This cardiologist in turn recommended that she needed a “dual lead” pacemaker instead of the single lead one she had. [It has been found that having more than one lead can sometimes improve the heart’s output for very carefully selected patients with heart failure.] When the PCP much later received the cardiologist’s mailed consult report, he disagreed, noting she did not have heart failure, just syncopal attacks – an electrical not a mechanical problem in her heart. Further, the current pacemaker was only needed about 10% of the time meaning that her heart beat at a normal rate at least 90% time, so the pacemaker was not even active most of the day. This lady did not need the proposed new, even more highly expensive pacemaker. No pacemaker, no procedure, no risk of insertion, no risk of post operative infection or bleeding. A lot of money could be saved and the patient could be spared a straight forward yet somewhat risky procedure – which she did not need. The fundamental problem was the lack of care coordination. One would like to believe that had her medical record been easily available digitally, the newly involved internist would have never even suggested the need for a cardiologist opinion and even if sent on, the cardiologist would have rapidly recognized the lack of need for the new device.
The lesson is one doctor needs to be the orchestrator of all of the patient’s care. A good PCP, like this one, coordinates the care of his or her patients with chronic illnesses and in so doing avoids excess referrals, tests, procedures and hospitalizations along with unneeded drugs or devices – all the elements that drive up the total cost of care – and in the process assures quality care, safer care and a close doctor-patient relationship. But sometimes a patient is elsewhere, sees a new physician and the medical history is not readily available. All too often as in this case, the patient ends up getting tests, images or procedures that he or she just does not need.
One of the most effective ways to reduce medical care costs is with good coordination of the care of individuals with chronic illnesses. As the story of Ellen above and of Henry from the earlier post exemplify, there is a strong tendency today for patients with chronic illnesses to either be referred to various specialists or else to go on their own. When this occurs without coordination, the visits add up, the number of tests and images ordered go up, the number of drugs prescribed rises rapidly and the number of procedures and even hospitalizations climb. Unfortunately, many of these are simply not needed – excessive and wasteful, not the best quality and obviously very costly. The value of a good digital medical record in both of these patients is obvious because communication among providers is critical to optimal care.

The primary care physician is in the best position to coordinate care. He or she knows the patient, the patient’s family and socio-economic situation and of course the patient’s various illnesses. Ellen did not need to see a second cardiologist and did not need the dual lead pacemaker. The PCP knew that “tired” was just her normal statement at every visit; not a reason to do more tests, add a drug or do a new procedure. It was unfortunate, indefensible but not at all uncommon that the new cardiologist did not make the effort to call the long time PCP. It would have been quickly determined that Ellen did not need a very expensive new pacemaker.

Henry suffered because he did not have a PCP. Instead he had four doctors, each one dealing with all of his problems and none communicating with the others. Once he had a single PCP, his prescriptions plummeted from 23 to seven, he felt better, had fewer drug-induced side effects and both he and his insurers were saving a lot of money.

Care coordination is critical; it improves the quality of care; it reduces risk; it reduces the costs of care; and it ultimately improves patient satisfaction. A good PCP (or occasionally a specialist) is needed to the orchestrator of that coordination. The electronic medical record has an integral part to play in robust care coordination.
Why, with all of these attendant advantages, do not all PCPs engage in excellent care coordination? I believe it is twofold – dollars and lack of training.

My new book, “The Future of Health-Care Delivery: Why It Must Change and How It Will Affect You,” from which this post is adapted, will be published in February, 2012 by Potomac Books

Care Coordination Is Critical For Those With Chronic Conditions Like Diabetes or Osteoarthritis

This is the fourth post in a series on care coordination; this time focusing on other examples of team-based care. Patients with diabetes not only have to deal with the diabetes itself and its management, such as insulin and drugs, but they have to deal with nutrition, weight and exercise. They need to cope with potential side effects of the diabetes, such as damage to their eyes or kidneys or the blood vessels running into the lower legs that can lead to ulcerations, infections and even amputations. The current approach is for an internist to be the patient’s primary care physician and then to send the patient on to a specialist whenever a problem arises. A much better approach is the one developed by the Joslin Clinic in Boston, which has now been “franchised” across the country. The internist refers the patients to a Joslin Center for consultation. There the patient has a nurse as their coordinator and advocate, an endocrinologist to work out the specifics of their diabetic drugs and insulin, an exercise physiologist to help them with an exercise plan, a nutritionist to review their dietary needs, an on-site ophthalmologist expert in diabetic complications of the eye, and a podiatrist to deal with foot issues. The point is that all of these professionals are available in a single location. The patient comes to one place and one place only and from there can go to individual adjacent offices to see whomever they need to see. Whenever they come back to see, say, the exercise physiologist, if there is an issue or problem they immediately can be referred across the hall to the appropriate specialist. They key is that these healthcare providers are all working as a team and bring to bear all of the different disciplines necessary to the treatment of this complex and complicated disease for this individual patient. And by using an electronic medical record, the data is all present all of the time as the patient goes from one provider to another within the Center but also back home with his or her primary care physician. The result is better care, more coordinated care and a much more satisfied patient. It also costs much less because there is less duplication, less unnecessary testing or X-rays, and fewer hospitalizations because the patient is better cared for.


So as time goes on, more and more of these disease-based programs will emerge for the care of complex, chronic diseases. To some degree this may seem to threaten the primary care physician in the community. But it is really a benefit and an adjunct to both the physician and the patient. The primary care physician still sees the patient for the bulk of their individual care but knows that he or she and the patient have an expert team available to help either occasionally or more often as necessary.

Here is an example of team based care in orthopedics. Marshall Steele, III, MD is an orthopedic surgeon in Annapolis, Maryland who did a lot of knee and hip replacements. He was frustrated that the system just was not efficient nor was it patient or provider friendly or convenient. So he and some collaborators worked with their hospital, Anne Arundel Medical Center, leadership to devise a totally new approach to total joint replacement. Briefly, it works like this. A unit of the hospital was set aside solely for total joint replacement patients with its own dedicated staff. A single leader who had full responsibility but also the needed authority was placed in charge, eliminating the traditional silos that exist in most hospital management systems. Instead of being focused entirely on the inputs which dominates organizations structured in departments, this new model focuses first on the outputs (outcomes) of their work from the perspective of all stakeholders. All patients for the week are brought in the week before to meet each other, meet the staff, tour the facility and attend a class taught by a nurse navigator or coordinator of what will transpire during their stay. They are then all brought to the hospital for surgery the same day, necessitating that extra ORs be available for the orthopedists. After surgery the patients are put into a wellness environment outside of their hospital room. There they are brought together for some meals each day and for beginning physical therapy. They even return as outpatients for physical therapy together.

These steps plus many others have markedly improved physician, nurse and physical therapist coordination and satisfaction while working as a multi-disciplinary team, each with their own expertise unleashed for the care of these patients. The patients are much more satisfied and work together as a support group. At a formal luncheon one month later, patient and family input is sought and programs changed to respond to their needs and those of their families. Length of stay is down and complications have been reduced. Important hospital reported metrics are collected and shared with the team on easy to understand electronic dashboards. Patient reported metrics are collected on how effective the procedure was in reducing pain and return to desired activities. As word got around, more and more patients, many from great distances, sought out the team. Hospital revenues rose and the orthopedists became very busy. Other hospitals have tried to emulate this approach. But many fail. Why? Because, as Dr Steele points out, what is needed is a transformational change but most physicians, hospital staff and hospital managements are only able to muster incremental change. Incrementalism where transformation is needed just doesn’t work.

As medicine becomes more and more disease/patient-oriented, the traditional departments of medicine and surgery within a hospital will tend to be de-emphasized and in their place will come centers for cardiac care, cancer care, diabetes care, stroke care, joint replacement and the like. A multidisciplinary team approach to care will become much more common. Just as with the primary care physician, this shift will appear to many practicing specialists to be a “threat” to their autonomy and certainly to their long-held practice patterns. To be effective they must have an effective electronic medical record system. Moreover, insurers do not like to pay for a team to see a patient. Their approach is to pay one physician for one consult or one patient visit. To pay for three doctors to see one breast cancer patient all at once is anathema, and, in general, they may refuse payment. Hospital managers, like physicians, are “conservative” and traditional, with functions organized in a format that was effective many years ago but which is no longer. But change is difficult and as pointed out in the story above on joint replacement, the change needed is transformational, not incremental. The electronic medical record, critical to success of these arrangements, must be part of the transformational change. Change will not come easily; but it must occur and so it will, but not quickly. But the hospitals who figure this out first will have a competitive advantage.

These stories raise the question as to why it is so difficult for physicians and hospitals to change their ways when the new approach can be shown to be so much more effective in delivering improved quality of care at a reduced cost?

My new book, “The Future of Health-Care Delivery: Why It Must Change and How It Will Affect You,” from which this post is adapted, will be published February 28, 2012 by Potomac Books. You can find it now at Amazon at http://tinyurl.com/

Lack of Care Coordination Leads to Patient Frustration and Poor Care

This is the third post in a series on care coordination and the importance of the electronic medical record to effect that coordination.

Medical images such as CT scans, MRI and pathology specimens are largely all digitized today so they can be transmitted to any location in an instant. This means that the most experienced physician at a distant institution can be called upon to review, say, a mammogram that has raised questions for the initial local reviewers or for a pathology specimen which is of an unusual type. It also means that when a patient goes for a specialty visit, his records could go simply and instantly and be available for the specialist(s.) This obviously will save time and improve patient care at limited increased cost. But it is largely not what happens today. Here is an example of what actually happens now.

A gentleman, I will call him Otto, who lives in a remote area in northern Pennsylvania developed a chronic cough. He went to his primary care physician, who diagnosed bronchitis and gave him a prescription for an antibiotic. But the doctor was clearly concerned and told Otto to “come back in two weeks if the cough is not gone.” Two weeks later, the patient returned unchanged. He was sent to the closest hospital, about an hour away, for a CT scan of his lungs. The result was not good; it looked like lung cancer. To definitively confirm the diagnosis he was told to come back in four weeks [!] for a biopsy to be done by inserting a needle into his chest. Why four weeks? Because the specialist at that rural hospital only did these biopsies every other Friday and he was booked up until a month later. So Otto had to be “patient” and came back as scheduled. The biopsy, sent to another hospital a hundred miles away for review, confirmed lung cancer. Now he was referred to a surgical specialist in yet another distant city, an academic medical center. That took a few weeks to arrange and, when he met the doctor, he was told that to make a good plan for treatment it would be necessary to get a PET scan. “OK,” he said, and it was arranged for two weeks later – the PET center just down the hall being booked up until then. So he drove home and then back two weeks later. Once the scan was done, a call came from the surgeon’s office that his return appointment had to be postponed for a month since the surgeon would be out of town. His wife, protesting that that was too long to wait, arranged for a visit to be “fit in” in two weeks rather than four.

By chance we happened to visit them that day and heard his story. I called my former University of Maryland Greenebaum Cancer Center colleagues and was told that he could be seen concurrently by a team of surgeon, radiation oncologist, medical oncologist and nurse practioneer in just three days time. But he would need to bring his medical record, his CT scan, the PET scan and the pathology report. So he had to call and then drive to each of the hospitals and pick up the materials. What he picked up were not pictures or films but CDs of his CT and PET scans and his pathology report; in other words they were already in digital format. Too bad these hospitals were not yet capable of just sending them via the Internet to the cancer center in the third city. This is supposed to be a story about the problems of getting information from one physician or hospital to another, but you will have also realized that it was about remarkably less than good care for him – waiting weeks to get the biopsy, more weeks to get the PET scan and then the absurdity of being told he could not be seen by the surgeon for another four weeks. What Otto needed was a well-coordinated, team-based approach to care, which he eventually got – but which he certainly should have gotten long before. This happens all too often in American medicine today.

This is the typical way most patients get treated for cancer (and most other chronic illnesses.) Go to one doctor and then once he or she is done with his/her recommendation, get shunted off to the next physician, and then the next, etc. The patient may be sent to another physician for a “second opinion” but never do the doctors actually sit down together and talk through the issues. When a team jointly discusses the patient’s situation, jointly listens to the patient’s (and family’s) needs and then jointly offers a plan, you can bet that the plan will be far superior – and there is not second guessing later. And as treatment progresses, the team can monitor progress and make course corrections as necessary. The multidisciplinary care coordination approach is not just better, it is far superior. If you develop a chronic illness and your doctor wants to refer you to a specialist, insist on a team-based approach.

Sharing information is a critical element of this approach. Today hospitals (and doctors) do not share medical information among themselves readily, such as when a patient is discharged from one hospital but then ends up in the emergency room of another hospital days or weeks later. Similarly, if a patient has a test at one hospital but then is referred to another for a procedure, it is nearly impossible, as we have seen in the story above, to electronically send that data from hospital to hospital. Instead, the patient usually has to act like “Federal Express” and pick up the information and hand deliver it to the other location, just like Otto. Not a good arrangement – it takes time and it only adds to the patent’s sense of anxiety when the systems should be working to reduce patient angst. Once the electronic medical record is available on a universal basis this difficulty should be abated. Meanwhile hospitals that determine how to share information now will find that they are benefiting patients and in the end benefiting their institution. They will be recognized as providing better care and be rewarded with patient referrals.
But this story raises the question as to why with the information in digital format and the Internet ubiquitous that records like Otto’s cannot readily be transmitted today?

Mesothelioma – A Poorly Understood Cancer

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.

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?

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?

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.”

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.

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.

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.

Mitral Valve Repair Without Open Surgery – Exciting Development in Medical Devices

The mitral valve separates the heart’s left atrium from the left ventricle. When the ventricle contracts to send blood to the aorta and out to the body, the mitral valve closes to prevent blood rushing backward into the atrium and back to the lungs. The mitral valve can become stiff and tight, called stenosis or it can become unable to close tightly, called regurgitation. Once the regurgitation becomes sufficiently severe to cause heart failure, the death rate reaches about 5% per year. Most such individuals are referred for cardiac surgery to either try to repair the valve, replace the valve or do a procedure that in effect lessens the amount of regurgitation without actually replacing the valve. The latter procedure, although not curative, can be quite successful and alleviate the heart failure and the symptoms leading to a longer and better quality life.

A new procedure has now been reported in the New England Journal of Medicine, April 14, 2011 that does not use open surgery to repair the mitral valve leak. The process is to insert a catheter via the large femoral vein in the groin and pass it up to the heart. From the right atrium it crosses over to the left atrium and then is positioned at the opening of the mitral valve. This mechanical device, manufactured by Abbott Vascular, is able to grasp the two sides of the mitral valve and clip the two leaflets together. It does not create a tight seal but in most cases can markedly reduce the amount of regurgitant flow back into the atrium.

The study randomly allocated patients with grade 3+ or 4+ (i.e., serious) mitral valve dysfunction to either the customary open repair or replacement (the specific procedure at the surgeon’s discretion based on the valve status) or to have a percutaneous repair done with the new device. The study endpoints were freedom from death, freedom from surgery for mitral valve dysfunction and freedom from grade 3+ or 4+ regurgitation at the end of 12 months. The primary safety end point was freedom from major complications during the 30 days post procedure.

The study ws performed at 37 institutions in the United States and Canada. 279 patients were randomized with a 2:1 ratio of percutaneous vs. open procedures. 21 patients withdrew consent before the procedure was done, leaving 258 treated patients.

After the procedure, 41 of 178 (23%) patients who had the percutaneous procedure still had grade 3+ or 4+ regurgitation and were therefore referred for open surgery. Among those 80 patients who initially had open surgery, all had less that 3+ regurgitation after the procedure. By the 12 month end of study time, the composite of freedom from death, from surgery or from grade 3+ or 4+ valve dysfunction for all randomized patients were 55% vs. 73%. If one looks only at those who actually were treated per the protocol (i.e., did not exclude themselves, etc) then the rates were 72% vs. 88%. As to safety, the rates of major adverse events (most often the need for transfusion) as of 30 days were 15% vs. 48%. Quality of life improved in both groups of patients over the 12 months although there was a decrease at 30 days for the open surgery patients.

What these results suggest is that open surgery is more likely to greatly relieve the mitral regurgitation than will the percutaneous catheter procedure. However, the percutaneous procedure is safer, requires less time in the hospital, and is associated with improved quality of life and improved ventricular function from baseline. Many patients might therefore decide to choose the percutaneous catheter-based procedure on the grounds that it greatly relieves the problem in almost three quarters of the patients, is less invasive and is safer than surgery. Then if that individual patient was not among the success stories, he or she can choose to have the follow-up open surgery.

Further, although not mentioned in this article, there are patients who simply cannot tolerate open surgery for any number of reasons who might still be able to undergo the catheter-based procedure. This might then open up an option for repair not otherwise available today with open surgery. Not discussed in the article was cost. This might become a deciding factor as well once the procedure is on the market.

In an accompanying editorial, Otto and Verrier suggest that the decision on surgery (and which surgical procedure) or one of a number of catheter-based procedures (assuming logically that others will undoubtedly arrive soon) should rest on the advice of not one physician but the joint opinion of a multi-disciplinary team of, at least, a nonprocedural valve-disease specialist, and interventionalist cardiologist and a cardiac surgeon, each with substantial expertise in mitral valve disease. To this team I would add the patient’s primary care physician and principal cardiologist – both of whom will have known the patient and his or her overall health and family situation over the years. The other addition to the team is the patient --whose opinions should be incorporated from the beginning of the evaluation and advice process.

Ultraprocessed Foods Lead to Chronic Illnesses

Much of today’s foods are “ultraprocessed,” lead to obesity and its ultimate diseases such as diabetes, coronary artery disease, hypertension, many cancers and worsening of diseases such as osteoarthritis.

Ultraprocessed foods originate from just a few grains, namely corn, wheat and soy but these then undergo extensive chemical and mechanical manipulation resulting in compounds that humans have never eaten before. Just look at the ingredients list on many store products and notice first how many ingredients are listed and second how few of them you recognize. Further they are concentrated as to sugars, salt and calories while deficient or totally lacking in the fiber, micronutrients and phytochemicals found in fresh or frozen grains, vegetables fruits and unadulterated meats and fish.

David Ludwig MD, PhD of Boston Children’s Hospital wrote a cogent article on ultraprocessed foods in the April 6, 2011 edition of the Journal of the American Medical Association and upon which the proceeding was based. He explains that there have been three major breakthroughs in food technology. The first came perhaps 2 million years ago with the development of stone tools and the use of fire for cooking. This allowed the human who did not have the running speed of large carnivores nor the digestive tract attributes of herbivores like cattle and sheep to expand his diet. The second big technology breakthrough was domestication of grains – agriculture. This led to civilization in the sense of larger more stable communities because domesticated grains such as wheat and corn greatly increased calories available and no longer required migration to hunt or gather. He makes the interesting observation that human stature dropped a few inches with this change because grains carry fewer micronutrients and protein per gram than do animal meats and nuts.

The industrial Revolution was the third breakthrough technology which led to refined flours and concentrated sugars along with grain-fed rather than grass fed cattle, sheep and hogs. Such animals are heavy with saturated fats although their protein content and ready availability has resulted in a return of greater stature in recent generations. More recently have come ultraprocessed foods.

These ultraprocessed foods are high in calories from sugars and fats – often hydrogenated and trans fats – yet low in micronutrients. They are found in supermarkets’ “middle aisles” as processed foods such as cereal with added sugar, cheese “spreads”, “macaroni and cheese,” soups high in salts and calories, “sticky buns,” and of course sugared sodas. And ultraprocessed foods are readily available in many fast food outlets where a muffin may have 400 calories with high contents of sugars and saturated fats. A bacon cheeseburger, large fries and large soda can contain well more than one half of a day’s caloric needs yet be deficient in nutrients.

Ludwig concludes with “the problem is the creation of a dietary pattern based on factory-made, durable, hyper-palatable, aggressively marketed, ready-to-eat or heat foodstuffs composed of inexpensive, highly processed ingredients and additives. Reducing the burden of obesity-related chronic disease requires a more appropriate use of technology that is guided by public health rather than short-term economic benefit.”

What can we do? We need to cut back on the ingestion of these ultraprocessed foods. But this will not be easy. For this to work I believe we need incentives. After all, that bacon cheese burger tastes good – sugar and fat are pleasing in our mouths. So we need more than just knowledge that we are eating well and thereby preventing future disease while improving our health. Knowledge is important because most people just do not realize the extent of the harm that comes from over consumption of ultraprocessed foods. With knowledge we can follow the advice of Pollan in his “In Defense of Food” to never buy a product that has more than five ingredients or has ingredients that we have never heard of or cannot pronounce. But knowledge alone is just not incentive enough to overcome the temptations.

Some thoughts: Government can help with how it subsidizes agriculture, incenting the growth of a broader array of crops and not marking the fattest meat as “prime.” And it can continue to insist that restaurants, especially fast food outlets, display calorie counts. Business can help with wellness programs that reduce the employee share of health insurance premiums in return for weight reduction or exercise programs. Insurance can offer incentives as well. Schools can offer only quality foods – good in itself but also a lesson in good dietary habits for our children in their formative years. And we each need to create our own incentives – as I typed this I also ate a chocolate chip cookie. I enjoyed it but have set myself a limit of one per day. My treat for finishing this blog post.

Surprise – Adolescent Obesity Leads To Later Heart Disease and Diabetes

Well, probably not a surprise at all. The seeds of coronary artery disease (CAD) are laid down early and over long periods. But given our current pandemic of obesity beginning in childhood, should we worry about an epidemic of chronic disease like diabetes and CAD in the years to come? The clear answer is a resounding “Yes.”

There has been a long term study of military men in the Israeli Defense Force. An article in the New England Journal of Medicine, April 7, 2011 reports on what happened over an average follow-up of 17 years after army induction at age 17 for those who chose to remain in the military after the required three years. This amounted to 37,674 healthy men followed for about 650,000 person years. Among them, 1173 developed diabetes type 2 over time and 327 developed angiography-proven CAD. All by the age of 45.

Here is the baseline data:

Blood pressure, resting heart rate, fasting blood sugar, and low density lipoprotein (LDL – the “bad stuff”) and smoking incidence progressively increased with increasing BMI (BMI, a calculated ratio of weight and height) among the 17 year old inductees. High density lipoproteins (HDL – or the “good stuff”) declined as did the amount of weekly exercise with increasing BMI.



Here is the follow-up data:

Since this was a study of men beginning at age 17 and lasting an average of 17 years, it follows that the 327 cases of CAD and 1173 of diabetes were among relatively young men – aged 25-45 years old. When the investigators adjusted for age, family history of CAD, blood pressure, smoking status, LDL, HDL and triglycerides they found that an elevated BMI at age 17 was a significant independent risk factor for CAD. Indeed the risk increased by 12% for each increment of 1 unit of BMI. They also noted that CAD occurred even in those with BMIs that are generally considered within the acceptable range today.

BMI at age 17 also predicted for the later development of diabetes mellitus type 2 (DM) with risk increasing about 10% for each additional 1 unit of BMI. But with diabetes, it was the adult level (age 25 and beyond) that was associated with a greater increase in diabetes relative risk. Said differently, higher levels of BMI at age 17 correlate with higher risk of CAD and diabetes in early adulthood. Persistent elevations of BMI increase that risk. Elevation in early adulthood increases the risk of DM during early adulthood whether or not the person had a higher BMI at age 17.

My takeaway:

It is imperative to intervene now in the growing pandemic of childhood and adolescent obesity. Even modest increases BMI can predispose to later CAD and DM. Once developed, these are chronic illnesses that persist for life, are challenging to manage, are expensive to treat and have a high impact on both quality of life and longevity. Our children are our future; it is our obligation to protect them. And if that is not reason enough, then think of your wallet. The high costs of their care will have a very significant impact on each of us in our taxes and our insurance premiums.

Bringing Down the Costs of Medical Care

It is currently popular for government officials to single out the insurance companies for the rising cost of healthcare. Not that the insurers are without fault but the real reasons for cost increases are rarely addressed and therefore not appreciated. We are a country with an aging population (“old parts wear out”) and of many adverse behaviors (e.g., overweight, sedentary lifestyle, stress and 20% still smoke.) Combined, these are driving a rapid increase in chronic diseases such as diabetes type 2, cardiovascular disease including heart attacks, heart failure and strokes, high blood pressure, and cancer.

These are illnesses that, once developed, are usually with the individual for life, have a major impact on quality of life and are inherently expensive to treat. The Milken Institute did a comprehensive study of chronic diseases. Among their findings: 109 million Americans have a chronic illness now [that’s about one third of us!] and many have more than one for a total of 162 million. The costs of care today are about $275 million and the total economic costs are well over a trillion dollars per year in lost productivity, etc. They estimate that we are on a track for a 42% increase in these chronic diseases by 2023 (as a result of aging and behaviors,) not that long from now. And if we do nothing to change the way we care for these patients, the costs of medical care will be $790 billion and the total economic costs will be over 4 trillion dollars.

There are two things to do to reverse this trend. These are illnesses that by and large are caused by our behaviors or are the result of aging. We can’t stop aging. So, the first step is to have an active program in behavior modification. Easier said than done, of course but here are some principles. We need to individually accept responsibility for our own health. But we need to understand what we are doing and how it impacts us over the long term. Government can help here with educational programs, rules about school lunches, requiring restaurants to post calorie and fat contents, labeling food packages with a more realistic total calorie assumption (today packages imply that the average person needs a 2000 calorie diet) and other steps. Incentives, primarily monetary ones, can have a big impact. Incentives need to be large enough to be useful yet focused enough to drive toward the desired end. Our employer can help with wellness programs to assist us to stop smoking, loose weight, improve our nutrition or deal with stress more effectively. The incentive here can be asking the employee who is successful to pay a lower portion of their health insurance premium. Insurers can create incentives directly for following a healthier lifestyle by lowering premiums for those who don’t smoke or are at a reasonable weight.

The second major step is to ensure that those who do have a chronic illness get very good care coordination. Unfortunately, this is just not the case for most patients today. They end up with multiple doctors, each doing their own thing, excess specialist consultations, too many medications, unnecessary tests and procedures and sometimes even unneeded hospitalizations. This drives up the cost of care dramatically. When one has a primary care physician that takes the time to fully coordinate all the elements of care, the use of specialists declines as do tests, procedures and hospitalizations and drug therapy is well managed.

Unfortunately, most primary care physicians have too many patients under their care to allow adequate time for prevention sessions or the time needed for care coordination. They need to care for fewer patients meaning they will need to receive a higher fee for each visit and this must include a reasonable payment for preventive activities and coordination efforts. Added to this they need to be paid to take the time to respond to emails and to use other technologies that can keep the patient out of the office unless really necessary. Some docs are doing just this by limiting their practice to about 500 patients (rather than the usual 1200-1400) and charging a flat fee for all care for a year. Others are refusing to accept insurance, both commercial and Medicare, and instead are billing the patient just as a lawyer or accountant or other professional would. The billing includes time spend in prevention and coordination. These may well be the future of primary care reimbursement and a means to assist the patient to first prevent chronic illnesses from occurring and second to assist in good coordination of the care when one does develop.

But all of this raises critical questions. What should and what will government do to help us modify our behaviors? Will insurers be allowed and will they accept the responsibility of a two tiered premium pricing system? Will employers accept the added chore of developing wellness programs? Will physicians, even if they are offered adequate payments, actually spend the time needed for good prevention and good care coordination? And, most importantly, will we as citizens accept our responsibility to lead a reasonably healthy lifestyle?