Friday, March 23, 2012

Use It or Lose It: The Price of Inactivity

Do you need a good incentive to exercise? Check out this set of pictures. They may well surprise you.

We all know we should exercise. It feels good during and we feel even better after. We know it burns calories and that our bodies were meant to be used. But all too many of us are sedentary; it just the result of modern life. One result, combined with eating too much, is that one third are overweight and one third are frankly obese. And many of us believe that as we age we will just naturally loose muscle mass and strength. It turns out that is just not correct. We can indeed preserve muscle mass and strength.
A really well trained athlete has little fat in or around his or her muscles. But a person that does not exercise sees his muscles wither and fat take up the space. That is the obvious conclusion from the images shown below.
More and more Americans are living into what used to be called “old age.” With older age often comes various illnesses, many of them chronic such as diabetes, heart failure or cancer. But these chronic illnesses are often preventable with a good diet and moderate exercise. So to is the “sarcopenia” or muscle loss that comes with aging in a sedentary person.

Wroblewski and colleagues at the University of Pittsburgh evaluated persistent exercise over the years. Their study was reported in The Physician and Sports Medicine journal, September, 2011 and sent to me by Frank Jannotta of Harbor Physical Therapy.

Five men and 5 women were recruited in each 10-year age category (40–49 years, 50–59 years, 60–69 years, and ≥ 70 years). Each was an avid exerciser. They were evaluated for their health history, exercise patterns, body composition using the “Bod Pod” and MRI scans of the thighs. The researchers found that despite the age differences, these individuals did not have a significantly different amount of intramuscular adipose tissue; their body fat, BMI, fat mass and muscle mass were all similar. Clearly, continued exercising into the 70’s maintained muscle mass in these individuals.
Here are three images taken by MRI scanning, i.e., a cross sectional picture. They are of the upper leg to show the quadriceps muscle, the large muscle on the front of the thigh that allows us to lift our leg and bend our knee when we walk or run.

The first image is of a 40 year old triathlete. The second is of a 74 year old sedentary person. And the third is of a 70 year old triathlete. The differences are obvious. Use it or lose it. Muscle to flab.

This proves that being older need not mean having no muscle tone. The difference between the two triathletes and the sedentary 74 year old are striking. It is clear that even an older person who exercises can maintain good muscle tone. And although this is of a triathlete, just good regular activity that combines both aerobic and weight bearing exercise will maintain those muscles up to the very last breath. And it means better health, long life, and much less chance that a fall will lead to a broken bone.

Use it or lose it. Here is the proof.

Sunday, March 18, 2012

Four Drugs – Each Creating A Tough Dilemma

For a parent of a child with cystic fibrosis, a new drug that could eradicate symptoms could be a God send. The same could be said of a parent of child with Angelman’s syndrome. For a patient with lung cancer, a drug that is more than marginally effective would be wonderful. And for a person with early Alzheimer’s or their loved ones, a drug that might actually reverse the disease would be incredible.

New drugs are approved by the Food and Drug Administration (FDA) regularly. Some are modest improvements over older drugs but some are true game changers. Some drugs approved for specific indications in the past are found to be useful in other conditions or situations. Some only work in very specified subgroups and some look promising in animals but have not been tested in humans yet. And many new drugs are very expensive. Four drugs are good examples that raise dilemmas. One dilemma is whether or how to pay for a very expensive medication and the other is whether one should consider using a drug, approved for another indication, if in an animal model of a serious condition it holds promise but has not been properly vetted in human clinical trials nor approved for this indication by the FDA.
Cystic fibrosis affects about 30,000 Americans. It is generally fatal by the mid-30s’. Genomic mutations lead to defects in the cystic fibrosis transmembrane regulator (CFTR) protein thereby preventing water and chloride from passing through the cell membrane resulting in thick viscous secretions that clog lung tissues. There are multiple CFTR mutations that cause cystic fibrosis. One of them, G551D, is present in about 4% of patients (about 1200 in the USA) with cystic fibrosis. Vertex Pharmaceuticals, Inc. has produced a compound called ivacaftor (Kalydeco) which has recently been approved by the Food and Drug Administration to partially correct the cystic fibrosis defect in this and only this subgroup of CF patients. It is a true game changer. But the price is nearly $300,000 per year and it will be needed for a lifetime. What does a parent do who does not have excellent insurance, any insurance or whose insurance requires hefty co-pays?
Lung cancer affects about 200,000 Americans per year. The drug erlotinib (Tarceva) was found to be effective in a small number of patients, generally among those whose tumor expressed the gene EGRF; it is these patients and only these patients who get the substantial responses. It’s a real advance in a disease that has been stubbornly resistant to treatment. But the drug is likewise very expensive, on the order of about $90,000 for a full treatment cycle. Improvements are real but still short lived. Is it worth it? This same dilemma pertains here as well. The patient will still die in relatively short order. What if paying for such a drug depletes a spouse’s financial reserves; should they decide to proceed with the treatment of not?
Alzheimer’s is of course very common (about 5.4 million in the USA today) and as the population ages there will be more and more individuals affected. There are some drugs available today but in general they are of little value in slowing progression or reversing memory loss. Now there is real excitement that a drug marketed for a completely different condition might be useful. The cancer drug bexarotene (Targretin), given orally, had a major impact on mouse brain cells while rapidly improving memory. Apparently it activates a gene that produces apolipoprotein E (ApoE) in the brain. The ApoE helps remove the beta-amyloid thought to be the substance that creates the plaques of Alzheimer’s. The plaque in these mice were reduced by 50% within 72 hours and by 75% within two weeks. (Science, February 9th). Clinical trials will be underway to determine if the drug will work in humans and if so, in what dose and timing. There is an old adage that results in mice do not necessarily predict results in humans. As a general rule, a physician would be loath to recommend using an untested drug in such as situation. But would a patient or the patient’s loved ones push for trying it out now, even before clinical trials are completed?
Angelman’s syndrome is a disorder in which there is a genetic mutation of the maternal Ube3a gene on chromosome 15 such that it is not expressed. The paternal gene, although normal, is suppressed in its action. The clinical result is a developmental disorder with speech impairment, reduced intellectual capacity, movement disorders and usually a happy demeanor expressed with frequent laughing. A report in Nature (December 21, 2011) demonstrated that topoisomerase inhibitors could activate (unsilence) the normal parental Ube3a gene in a mouse model. Among the active topoisomerases were topotecan and irinotecan, each approved by the FDA for treating certain cancers. As for Angelman’s syndrome, clinical trials are just beginning to determine if the mouse data can be replicated in humans and, if so, what is the best dose, route of administration and length of therapy. As with bexarotene and Alzheimer’s disease, this will take years to complete. So if you are a parent, do you quietly sit back and wait or, even though there is not human data, do you press your physician to give one of these drugs a try on your child?
The dilemma surrounding cost of new drugs is becoming more and more acute. There are now many drugs that are quite expensive, well beyond nearly any individual’s financial means to pay for them themselves. In general this is because a number of new drugs are being produced not for a mass market (such as statins for lowering cholesterol or a drug to lower blood pressure) but for a very small market such as the examples with cystic fibrosis and lung cancer where the drug is used for only a small subgroup of patients. The possibility is real that a family simply cannot afford the drug or that it will reap havoc with the family’s finances for years to come.
The dilemma about whether to try using a drug not approved for a disease at hand such as Alzheimer’s or Angelman’s syndrome yet on the market for another condition is equally vexing. Good clinical science says not to do so. But for the patient or patient’s family when the situation is grim, the desire is to plow ahead. The problem is that there are often reports in the press based on laboratory science that suggests a possible breakthrough. But it is equally true that most of these do not pan out when tested in the human situation. Carl Zimmer in the Wall Street Journal on March 10, 2012 wrote of Jackie Fenn’s “Peak of Inflated Expectations” that is all so often followed by the “Trough of Disillusionment.” And that could well be what happens here as these drugs are tested in human clinical trials.
The kids with CF that get Kalydeco will have a great benefit; those with lung cancer that receive Tarceva have a good shot at some meaningful benefit. Both will pay a hefty price. But for those with Angelman’s syndrome or Alzheimer’s, the possibilities for improvement are likely a long way off.

Comments from readers about both of these dilemmas are invited.

Friday, March 9, 2012

Gait Speed As A Medical Measure Of Vitality

As a person ages, we notice that some seem frail early in life yet others continue as vital for decades. Is there a way to detect frailty onset or even potential lifespan? There may be with a simple gait test.

New research suggests that “gait speed” can predict survival. The test is simple. Have the person walk a four meter distance starting from a standing still position. Measure the time with a stop watch. Speeds of greater than 1.0m/sec closely associates with healthier aging. Below 0.6m/sec correlates with poor health and less functional capability. A breakpoint of about 0.8m/sec separates individuals who will survive for less than or more than the median. Over 1m/sec suggests better than average survival and over 1.2m/sec suggests an even greater survival advantage. These are from a Jan 5, 2011 publication by Dr. Stephanie Studenski and colleagues in the Journal of the American Medical Association.
Fragility may seem to be just a subjective observation but, as I posted previously, there is a real science to frailty measurement.

Those predicted to live another five to ten years or more might be given greater consideration for preventive measures that normally take years to achieve a benefit. On the other hand, those with high risk for a short life span might be considered further for what modifiable circumstances could be adjusted to the patient’s benefit.

The data for these analyses were from nine studies conducted from 1986 to 2000. Each study had over 400 older participants, each community dwelling, whose gait speed was recorded and then followed for survival for five plus years. The graphic will illustrate the findings.

Here is a short video; click here and then click on "Walking Speed"
JAMA Report Video
And for a graphic of the results go here

These data help to differentiate the old (based on age) from the geriatric (based on biology). In an accompanying editorial, Dr. M. Cesari points out that not only is it useful to make this differentiation in older individuals but in other groups as well. For example in oncology practices, it is well known that performance status predicts outcome. Restated, those with low performance scores should normally not be treated with aggressive chemotherapy (the exception is in certain well defined situations) because the side effects are likely to outweigh the possible benefits. Surgeons, likewise, need to know who might be likely to encounter an adverse outcome. Gait speed might prove a useful way to select out who should likely not have chemotherapy or who should likely not have elective major surgery. Cesari points out that gait speed is not just a measure of leg function. It probably is a marker of a generalized physiologic function that correlates with health status.
Gait speed may become a marker to differentiate the chronologically old from the functionally geriatric. Check out your own rate.

Wednesday, March 7, 2012

Misconception – Healthcare Reform Will Impact Medical Science

Many harbor the concept that the recently passed reform legislation – The Patient Access and Affordable Care Act – will mean even greater advances in medical science. This is a misconception.

The reform bill is all about access to care – getting those without insurance to get insurance either through the commercial market place or through Medicaid. This will create at least 31 million more individuals with Medicaid, will keep young adults on their parent’s insurance for a few more years and will prevent a person from being denied insurance as a result of a previous condition and will mean that an insurance company cannot drop a patient because the expenses got too great over time.

The reform bill will also begin a process to evaluate the best care available based on sound scientific evidence. And it will sponsor many pilot projects to find better methods to effectively deliver care.

But it will not have any appreciative impact on the advance of science. That is not a problem however because America is the envy of the world for its biomedical science research. This is funded primarily by the National Institutes of Health (NIH) and conducted by scientists and clinicians in medical schools and universities across the country. Their output has been awesome and will continue to be so.

The pharmaceutical industry is likewise very productive in bringing forth new drugs which save lives, add years to lives or impact the quality of life. A good example is the recently approved drug for certain patients with cystic fibrosis. Likewise the medical device industry is exceptionally innovative and entrepreneurial. For example in cardiovascular disease it has over the years created angioplasty and stents, pacemakers and intracardiac defibrillators (ICDs), monitors for arrhythmias, even the replacement of heart valves without surgery. It is both amazing and impressive. So too the manufacturers of imaging equipment such CT and MRI scanners and ultrasound scanners that can show our internal anatomy in exquisite detail and do it all non-invasively. Now also external scanners can detect metabolic changes within our tissues; for example, PET scans to detect cancer.

And then there are the treatment devices such as the truly remarkable new approaches to radiation therapy that allow greater radiation to the tumor but much less to the surrounding normal tissues.

The marriage of genomics and molecular biology with diagnostics means that it is now possible to detect a bacterial infection rapidly and even know what antibiotics will be or will not be effective within just an hour or two. It is possible to subtype patients with, say, breast cancer, as to who is more likely to have a recurrence and therefore adjust her therapy upfront and it is increasingly possible to determine in advance who will and will not respond to a specific drug and who is most likely to have a side effect to that drug.

These advances will continue as a result of the government funding of the NIH grants program and because the pharmaceutical and device makers have found it profitable to develop new modalities. The future here is bright. But we should not mistake these incredible programs as a result of the health reform legislation. You can read more in my new book "The future of Health Care Delivery"

Praise for Dr Schimpff

The craft of science writing requires skills that are arguably the most underestimated and misunderstood in the media world. Dumbing down all too often gets mistaken for clarity. Showmanship frequently masks a poor presentation of scientific issues. Factoids are paraded in lieu of ideas. Answers are marketed at the expense of searching questions. By contrast, Steve Schimpff provides a fine combination of enlightenment and reading satisfaction. As a medical scientist he brings his readers encyclopedic knowledge of his subject. As a teacher and as a medical ambassador to other disciplines he's learned how to explain medical breakthroughs without unnecessary jargon. As an advisor to policymakers he's acquired the knack of cutting directly to the practical effects, showing how advances in medical science affect the big lifestyle and economic questions that concern us all. But Schimpff's greatest strength as a writer is that he's a physician through and through, caring above all for the person. His engaging conversational style, insights and fascinating treasury of cutting-edge information leave both lay readers and medical professionals turning his pages. In his hands the impact of new medical technologies and discoveries becomes an engrossing story about what lies ahead for us in the 21st century: as healthy people, as patients of all ages, as children, as parents, as taxpayers, as both consumers and providers of health services. There can be few greater stories than the adventure of what awaits our minds, bodies, budgets, lifespans and societies as new technologies change our world. Schimpff tells it with passion, vision, sweep, intelligence and an urgency that none of us can ignore.

-- N.J. Slabbert, science writer, co-author of Innovation, The Key to Prosperity: Technology & America's Role in the 21st Century Global Economy (with Aris Melissaratos, director of technology enterprise at the John Hopkins University).