Posts Tagged ‘stroke’

Will I live a much longer life than I expected?

Friday, May 20th, 2016

In April I became three-quarters of a century old. I am basically healthy and I'm in the gym six days a week although I've got five orthopedic/metabolic issues even after having a right total knee surgery fifteen years ago and three low back operations. The "Curse of the Springbergs'" back continues to plague me; a nerve in the left side of my neck is pinched from time to time; my right shoulder is intermittently painful; I have a trigger finger on my dominant hand and I've had, in the last four months three attacks of gout or perhaps pseudogout, where the crystals deposited aren't uric acid,, but a calcium compound. My recent blood test for my uric acid level was right in the middle of the accepted normal range; that doesn't mean the attacks weren't gout, but deterred my podiatrist from giving my a prescription for allopurinol which could potentially prevent further attacks.

On the other hand, my brain still works pretty well and I'm below my college wrestling weight, so I would potentially be interested in living a long life and treating those nagging, but admittedly minor ailments.

Most members of my family have lived to considerable ages, with only one self-inflicted exception (not suicide, just terrible eating habits resulting in gaining fifty pounds plus really poor adherence to medications prescribed). My mother died at ninety, my father was nearly ninety-five, his sister was ninety and three aunts on my mother's side lived to ninety.

So I was intrigued by an article that appeared in The New York Times recently titled "Chasing Immortality: Dogs Test Drug Aimed at Humans' Biggest Killer: Age. (1)

We typically think of people in developed countries dying, as my wife did in late December at age seventy-five, of a stroke, or as my brother (vide supra) did at fifty-seven, of a heart attack. Cancer, diabetes and Alzheimer's (and other dementias) are also common causes of death in our population, but the article pointed out that "treatment breakthroughs" for these maladies, although crucial for those affected, would likely increase our overall populations life expectancy by just a few years.

I looked at the reference cited in the article. It's a 1990 article in the journal Science and only the abstract is easily available, but its bottom line was even if we found cures for those "major degenerative diseases," it would only result in raising the life expectancy at birth to 85 years, not the Biblical 120, much less even longer life spans.

Now there's a canine trial of rapamycin, a drug first isolated in 1972 from a bacteria found on Easter Island and named after the native designation for that island, Rapa Nui. It was originally developed to fight fungal infections, but later used in preventing organ transplant rejections. It has been shown to increase lifespan in mice. Whether rapamycin slows down aging, however, remains unclear.  The life-extending effect seems to be related to rapamycin's suppression of tumors, which represent the main causes of death in in those animals. (2)

The early results in canines are promising, but the research reported is what's termed by the NIH as a Phase One study, a relatively brief test of a new drug in a small group of subjects to evaluate its safety, determine a safe dosage range, and identify side effects. Bela, the eight-year-old dog featured in the article may have been given rapamycin or may actually be receiving a placebo.

After Phase One we would have considerable time before humans got the drug in a clinical trial, much less having the drug available to your physician or mine for more general use. The dog studies would likely go through Phase Two and Phase Three studies; then there would be considerable discussion before a human Phase One test was started. And there are other phases to accomplish before approval of rapamycin for the purpose of life extension in our species. I copied and pasted definitions of those phases for you and added a few comments.

Phase II studies test the efficacy of a drug or device (Does it work for the particular purpose intended, in this case extending our life span?). This second phase of testing can last from several months to two years, and involves up to several hundred patients. Most phase II studies are randomized trials where one group of patients receives the experimental drug, while a second "control" group receives a standard treatment or placebo. Often these studies are "blinded" which means that neither the patients nor the researchers know who has received the experimental drug. (This is crucial since the hope is to eliminate the "placebo effect...I got the new medicine; I'm feeling better, so it must be from that drug. This is called  the "Post hoc, ergo propter hoc" fallacy. It happened after X, so it must have been caused by X. An extreme and silly example would be the sun came up and shortly thereafter I had a car accident, therefore sunrise causes car crashes.) A Phase Two study allows investigators to provide the pharmaceutical company and the FDA with comparative information about the relative safety and effectiveness of the new drug. About one-third of experimental drugs successfully complete both Phase I and Phase II studies.

Phase III studies involve randomized and blind testing in several hundred to several thousand patients. This large-scale testing, which can last several years, provides the pharmaceutical company and the FDA with a more thorough understanding of the effectiveness of the drug or device, the benefits and the range of possible adverse reactions. 70% to 90% of drugs that enter Phase III studies successfully complete this phase of testing. Once Phase III is complete, a pharmaceutical company can request FDA approval for marketing the drug. (This is the one we should wait for when we read early reports of a new medication that may help a medical issue we are afflicted with).

Fortunately, there is another phase, one that has a number of purposes that drug companies are interested in, but one that can protect our larger population, especially when the new use of an old drug leads to a much larger group of us being exposed to the drug.

Phase IV studies, often called Post Marketing Surveillance Trials, are conducted after a drug or device has been approved for consumer sale. Pharmaceutical companies have several objectives at this stage: (1) to compare a drug with other drugs already in the market; (2) to monitor a drug's long-term effectiveness and impact on a patient's quality of life; and (3) to determine the cost-effectiveness of a drug therapy relative to other traditional and new therapies. Phase IV studies can result in a drug or device being taken off the market or restrictions of use could be placed on the product depending on the findings in the study. (I underlined the last sentence, as this is a further protection for those of us in the general population, assuming we weren't lucky enough to be in a study group. I have a friend who had cancer, with a recurrence after surgery, but got into a Phase Three study and is now cancer-free.)

I found a list of 35 such medications, including Quaalude and Vioxx that have been withdrawn from the market in the last forty or so years. Quaalude is now a Schedule One drug, taking its place alongside heroin. Vioxx was implicated in over 27,000 deaths. (3)

It's a juggling act, to use a phrase that may seem inappropriate. What if rapamycin extended the life span of 98% of those who got it long-term, but severely damaged or even killed 2%. Would you take the drug under those circumstances? Would you want it banned from being prescribed?

What if, in extending human life span, it also allowed time for researchers to come up with treatments or even cures for that list of the major killing diseases?

Mull over those tough questions...we've got a few years before they need to be answered.

Links: (1)                                                                                                               (2)                                                                                                                                         (3)





Treating strokes in time: an update

Wednesday, June 26th, 2013
If you're having stroke symptoms, call 911 and get to the ER in a hurry

If you're having stroke symptoms, call 911 and get to the ER in a hurry

I've covered this territory before in a prior post, but there's compelling new data on this crucial health issue. In the June 19, 2013 edition of JAMA is an article titled "Time to Treatment With Intravenous Tissue Plasminogen Activator and Outcome From Acute Ischemic Stroke." The basic concept is that promptly getting someone who has suffered a stroke to a hospital that has modern "clot buster" therapy available markedly improves their outcome.

But in order to understand what it is that the research paper espouses, let's go back a few notches and work up gradually to the details of the paper.

I've always wondered why a stroke is called, in lay language, a stroke (physicians call it a CVA, a cardiovascular accident). The best answer I've seen is that someone who appeared to be in generally good health could abruptly be struck with acute neurologic symptoms: sudden weakness or numbness on one side of the body; sudden confusion, difficulty speaking or understanding; sudden loss of vision in one or both eyes; sudden motor problems (difficulty with walking, balance, loss or coordination or dizziness); or sudden severe headache without any known cause.

Most people (93%) recognize the first of those symptoms, the sudden onset of unilateral weakness or numbness, as indicative of a stroke, but less than 40% know all five major signs that a CVA is in progress. When you have one of the five, the CDC says you should call 911. You need to be at the Emergency Room within a realtively brief period of time to have an optimal chance of a best-outcome recovery.

What are your risk factors for stroke?

What are your risk factors for stroke?

The major risk factors for stroke are high blood pressure, high LDL cholesterol and smoking. The Stanford online article on CVAs mentions that all the usual cardiovascular threats can play a role, e.g., diabetes, obesity, lack of exercise, diet, stress. Oral contraceptives, especially those with higher estrogen content appear to increase the risk of blood clots, including those that may cause a strokes, particularly in women over 30 and post-menopausal estrogen use may somewhat elevate stroke risk.

Of course you can't change your age (some try) and two-thirds of strokes occur in those over 65. It's also about 25% more common in males and a positive family history of CVAs may be a factor. African Americans have twice the risk of having a first stroke as do whites.

The first more detailed accounts of stroke, referred to as apoplexy from the Greek word  ποπληξία, meaning struck down with violence, were written by Hippocrates (460 to 370 BCE) describing a sudden collapse, a loss of consciousness and paralysis.

The American Stroke Association has a great visual on types of strokes, listing three kinds: ischemic (lack of blood flow to the brain), hemorrhagic (the result of bleeding in that vital area of our bodies) and TIA (transient ischemic attack, a mini-stroke or warning stroke), but I also went to the online information sheets from the Stanford Stroke Center which has a comprehensive discussion of the ailment.

A stroke is sometimes called a "brain attack," presumably to underline its importance as equivalent to a heart attack . It is a leading cause of death in the United States, killing one of us in this country every 4 minutes and costing nearly $40 billion a year between health care, medications and missed work days.

Nearly 800,000 of us will have a stroke this year and 87% of all CVAs are of the ischemic type. As I've said before, "Time is Brain." You can lose 2 million brain cells every minute after the onset of a stroke.

Although the average age in large studies of CVAs is in the early 70s (actually 72, the age I'm at now), one third of all stroke victims are under the age of 65.

Prior studies with a protein called tissue plasminogen activator, a substance that can dissolve blot clots (and therefore termed a clot buster) have shown the possibility of minimizing damage from an ischemic stroke, but have been limited in size and therefore not having results as clear-cut as I wanted to see.

Now that limitation has been overcome by a very large-scale data set, the US national "Get With The Guidelines--Stroke (GWTG-Stroke) study. This is a combined project of the American Heart Association and the American Stroke Association, started in 2003 and involving 1,656 hospitals and over 2 million patents.

The JAMA article, looking at results of clot buster therapy in over 58,000 patients who had an ischemic stroke and got treatment in less than four and a half hours, had striking conclusions.Every 15 minutes slower from onset of symptoms to treatment worsened the eventual outcome.

Let's flip that around: the quicker you get to the ER the better are your chances of having a good result.

That means fewer deaths, fewer brain hemorrhages, better likelihood of walking by yourself and better chance you'll go home instead of to a nursing home.

It didn't matter what your age, gender or race/ethnicity was, the results were similar in all groups.

So remember (or learn) the five major symptoms: sudden weakness or numbness on one side of the body; sudden confusion, difficulty speaking or understanding, sudden loss of vision in one or both eyes, sudden motor problems (difficulty with walking, balance, loss or coordination or dizziness) or sudden severe headache without any known cause.

And if you have one of them, call 911 and get your brain to an ER by ambulance.

Bring the rest of you along to keep it company.

Stroke updates: new symptoms and old associations

Friday, March 22nd, 2013

Most strokes (AKA cerebrovascular accidents or CVAs) cause multiple symptoms and often develop suddenly, but in some cases you may be having a stroke and not be aware of it. The NIH website on stroke has lots of basic information that may be helpful; the most important fact, I think, is that stroke is a medical emergency. If you believe you're having a CVA, call 911.

The saying is, "Time is brain," in other words the more rapidly you can receive modern emergency stroke therapy, the more brain cells you can potentially save. The Mayo Clinic website has a through discussion of modern emergency therapy for stroke, but urgency is crucial.

We commonly think a person suffering a CVA suddenly loses feeling or muscular control in an arm or leg or one side of their body, but changes in alertness, hearing or taste, clumsiness, confusion, vertigo, loss of balance, personality changes, visual difficulties and a host of other symptoms/signs may also result from a stroke

Text messages should make sense.

Text messages should make sense.

Recently a new symptom has appeared, not dyslexia, a very broad term defining a person's fluency or comprehension accuracy in being able to read, but dystextia, the loss of ability to send coherent text messages. Two cases of this bizarre presentation of a CVA have been reported in the last four months. JAMA Neurology had a March, 2013 article concerning a previously-health 25-year-old pregnant woman, brought to an emergency room after sending her husband garbled text messages about the baby's due date. In retrospect she had encountered some difficulty in filling out forms during a visit to her Ob-Gyn physician and had also experienced a brief episode of weakness in her right arm and leg.

Her workup revealed other neurological signs and an MRI showed evidence of a stroke. Fortunately she had a rapid improvement and was given low-dose aspirin and another blood thinner for prophylaxis of leg clots (since she had an atrial septal defect (AKA hole in her heart) that could allow a clot to go to the brain. Her fetus suffered no harm.

Another person initially presenting with dystextia, in this case a 40-year-old man, was reported in a New York Times online article recently. By the following day the businessman involved had developed some speech difficulties and a CT scan showed an abnormality in a portion of the brain involving language production. So, in this era, with many people using their cell phones and their digits, but not their voices, to communicate, sudden development of garbled texting may be an early symptom of a stroke. It could be considered a form of aphasia, a condition that robs you of the ability to express yourself to others.

In October, 2010 the World Stroke Organization launched a "1 in 6" campaign" saying that's the proportion of us that will have a stroke in our lifetime. The statistics are grim: every six seconds a stroke kills someone, with estimates of 15 million CVAs a years worldwide resulting in 6 million deaths. In the United States, stroke is one of the leading causes of death with 130,000-140,000 fatalities a year.

Risk factors include high blood pressure, a family history of stroke, an irregular heart rhythm called atrial fibrillation, diabetes, race (blacks are more likely to die of a stroke), high cholesterol and increasing age.

In December, 2012, JAMA published an article titled "Sex, Stroke and Atrial Fibrillation." Before I go into the article itself, let's talk about the malady, AF for short. It's the most common type of abnormal heart rhythm, affecting millions of Americans, according to the NIH's National Heart, Lung, and Blood Institute. AF is caused by conditions (like high blood pressure or coronary artery disease) that damage the conduction system of  heart, its equivalent of the electrical wiring system in your house. The result is a heart rhyme that is the antithesis of being regular; it's irregularly irregular with heart beats coming at odd intervals.

The upper chamber receive blood and lower chambers pump it out

The upper chambers receive blood and lower chambers pump it out

During AF, the hearts upper two chambers, the atria, don't pump every bit of their blood to the lower two chambers, the ventricles. When that happens, clots can form and can migrate up to the brain, causing a stroke.

The recent article studied more than 83,000 patients over the age of 65 who were admitted to a hospital in Quebec with a recent diagnosis of AF. Slightly more than half (52.8%) were women and they tended to be somewhat older and had a more frequent history of high blood pressure, diabetes, congestive heart failure (CHF implies the heart doesn't pump as effectively as it should), and prior stroke or TIA (short-term neurologic changes suggestive of a stroke), than the men did.

The women in the study may have been older and had more co-morbid (existing) illnesses than the men, but even after statistically adjusting for these differences in the sexes, women had a higher risk of stroke than men did.

Why this was true is not known, especially since the study group contained women who were post-menopausal and therefore estrogen can't be the culprit. Current therapy with anticoagulant drugs, if such can be given safely, appears to be highly effective in preventing strokes in women with AF. New drugs are beig developed, but many experts in the field think the old ones have a reasonable safety profile and work just fine.

I have not read anything to suggest that most of us should be taking anything prophylactically to prevent stroke. About 85-88% of CVAs are ischemic (too little blood going to a portion of the brain), not hemorrhagic (caused by bleeding). If you've had a stroke already or a TIA, your doctor may recommend blood-thinning medication, but for the vast majority of us, controlling our risk factors, especially our blood pressure, appears to be the safest route to take.

Remember that phrase, "Time is brain." It's been estimated that only 29 to 65% of stroke victims utilize EMS in various communities. Yet for every minute a CVA is untreated you can lose 1.9 million of your brain cells.

So the phone is your best friend if you believe you're having a stroke.





What's the best way to prevent a stoke?

Tuesday, September 25th, 2012

The carotid arteries are a main line of supply for your brain

Last January the Center for Medicare and Medicaid Services convened a meeting to discuss what's the best way to handle carotid artery disease (CA-D). Those vessels are a major supply of blood to our brains and, as we age , smoke, don't exercise, have high blood pressure, diabetes, high cholesterol, get obese, or develop other risks factors they can be narrowed by atherosclerosis (AKA hardening of the arteries).

Obviously if we can stay young (we can't), keep our weight normal, have normal blood pressure (start by consuming less salt), and never smoke, we have a better chance of less changes in our blood vessels.

Well that's just not the case for much of our population, so then the question arises should our medical folk look for CA-D on a routine basis? Except for being 71 years old, I'm at relatively low risk with normal lipids, a weight approximating what my 8th-grade scale would have shown and a BP of 118/68. I only smoked for four years and quit for good over 40 years ago. So  my physician listens to my neck for an abnormal sound called a bruit, but otherwise hasn't suggested any other tests for CA-D.

How about the rest of her patients, or for that matter, all of you who are adults. If you have risk factors, and I should include a family history of stroke, you may or may not have symptoms of CA-D. Those could include, but aren't limited to, blurred vision, weakness in one part of your body, problems in speaking or understanding others, memory issues or being confused.

Then your physician has a host of tests she or he can order: those include an ultrasound to see if you have normal blood flow, angiograms, or even CAT scans or MRIs. Ultrasound (the fancy term is a carotid duplex Doppler study) is noninvasive, so nobody has to stick an artery or inject a dye. Angiograms, also called arteriograms are invasive and there's an added risk if the dye is can cause damage to your kidneys. CAT scans expose you to x-rays and MRIs may be tough if you're claustrophobic (although the chamber was much more open the last time I had one).

So most docs will be very judicious in picking which patients get which tests.

But what if you don't have CA-D symptoms and either physical examination or testing reveals significant disease? An Australian neurologist, Dr. Anne L Abbott has been a significant figure in opposing the current high rate of carotid artery procedures. Roughly 125,000 Americans per year have either carotid artery surgery or angioplasty with stent placement (inserting a balloon catheter  which is inflated to open the artery and a mesh tube designed to keep it that way).

This is what a vascular stent looks like


There's a heated debate going on among physicians who are experts in vascular disease and thirty-eight of them wrote an open letter to Medicare opposing the manufacturers who want the government agency to expand insurance coverage to include stent placement in patients who have no symptoms at present.

On the other hand, a May 2010 article by an interventional Cardiologist, Dr. Cristopher White from the Ochsner Institue in New Orleans, examines in great detail the results of a variety of studies done in the United States and in Europe. He mentions that stroke is our third leading cause of death; that of the 3/4th million who have one in this country per year, many are left with significant disabilities; and of adults over 65, one in twenty to one in ten have significant carotid artery narrowing (50% or more) without having symptoms.

Stroke risk is clearly related to how much atherosclerotic disease is present; more is bad. The article I mentioned above was written by and perhaps slanted toward stents and compares surgical and non-surgical interventional approaches. What is not clear is how much screening should be done in patients without symptoms and what the outcome of modern medical therapy would be compared to either invasive procedure.

I'm very interested to find out more, but have no intention at present of having more tests without better data.





What are those?