Why combination pills?

Almost half of the drugs marketed today are fixed combinations of two (or rarely more) drugs that are also available separately. In a very few cases, the use of such fixed-dose combination products makes sense. Examples would be many birth control pills, the urinary infection drug trimethoprim-sulfa (sold as Bactrim or Septra) or the Parkinson’s drug carbidopa-levoda. Here the two drugs help each other and work better together than does either alone.

Many more combinations are no better than using the two products separately but offer some convenience and so improve compliance – it is always easier to take one pill than two. The medical problem with many combination pills is that the doses of the two ingredients cannot be adjusted separately, and it is only by coincidence that the amounts in the pill might be correct for any given person. In the World Health Organization’s list of 240 “essential” drugs, only seven are fixed-combination products.

A major societal problem with many combination pills is the absurd over-pricing attached to the product. One horrific example is Vivimo, marketed for pain (and really being pushed hard to doctors as an alternative to narcotics). What is Vivimo? It has the anti-inflammatory drug naproxen (Aleve and others) packaged with esomeprazole (Nexium and others). The logic is simple. Naproxen, like all “non-steroidal anti-inflammatories (NSAIDs)” (ibuprofen, aspirin and numerous prescription products), can irritate the stomach. For long-term users of these products, or for people with prior stomach bleeding who still might benefit from their use, doctors may prescribe an acid-suppressor along with the NSAID. You can buy 60 tablets of naproxen, a month’s supply, for about $35, and for about the same amount get a month’s worth of an acid suppressor like esomeprazole. So, $60-65/month for the same ingredients as are in Vivimo. Vivimo was first marketed by Astra Zeneca. Horizon Pharmaceutical bought rights to the product in 2013, when it cost $57 for a month’s supply and immediately raised the price to $400. Nine price hikes later, it now lists for $1241 for a month! Why, you may ask, would anyone use this? Since Horizon is very skilled at gouging, as are most pharmaceutical companies, they use coupons to lower the out-of-pocket cost to consumers – but not to their insurance companies, which then just jack up premiums to cover the cost.

Another similar example is Zegerid, which combines the acid-suppressor omeprazole (Prilosec and others) with sodium bicarbonate (yes, baking soda) and sells this frankly silly product at a list price of $14,213 for a 90-day supply! Again, coupons lower the out-of-pocket cost to the consumer, but the cost to society and indirectly to the consumer are very high.

A group of Harvard researchers looked at Medicare spending in 2016 and found that Medicare spent $925 million more for combination drugs than would have been spent on the products bought separately. While this is a small fraction of the enormous waste in our bloated healthcare system, it should be one of the easiest to fix. Just say no to fixed combinations in most situations.

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Green - the color of relief

This post was originally going to be about the waste in the U.S. health care system, but it is Christmas and Hanukah, and who wants a downer story at the holiday season?

Serendipitously I came across a “do you believe it?” story that was much more fun to write. Several research groups, notably at the University of Arizona and Harvard, have found that exposure to green light can relieve pain. The Harvard group found that while most migraine sufferers cannot tolerate light (the medical term for this is photophobia), green light is much less annoying than other colors, and may even relieve the headaches. The group at Arizona found 2-3 years ago that rats exposed to green light were much better able to tolerate heat on their paws than rats exposed to other light or left in the dark. It has also been found that people who are surrounded by greenery are healthier than others. I assumed this reflected a generally healthier environment and lifestyle, but who knows. There is some experimental data suggesting that green stimulates the body’s own (“endogenous”) opioid system.

Dr. Mohab Ibrahim, the lead researcher at U Arizona has recently done a small study with 25 chronic migraine sufferers who had numerous headaches that interfered with their quality of life. They spent two hours daily in a dark room exposed to green lights, and all had major improvement in the frequency and severity of their migraines. Some got relief within a few days of starting while in others it took weeks. All had their usual headache pattern return when the light treatment was stopped.

Since sitting in a room looking at green light two hours a day is hardly convenient, alternatives are being studied. One (totally uncontrolled) study has found that wearing green-tinted eyeglasses has a beneficial effect on relieving chronic pain. While I am a great skeptic when it comes to “alternative therapy,” using green to help relieve pain appeals to me. It is cheap, it is totally safe, and it has just enough data behind it to be plausible.

Try it – you just may like it. Happy holidays.

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What's the truth about vaccination?

A headline I should never have had to see: “Worldwide measles deaths surge, reversing years of progress.” This was ABC News on December 5, quoting a report from the World Health Organization that over 140,000 people died in 2018 from measles, most children under 5. The same week, officials in Samoa asked the public to hang red flags outside their homes if they had an unvaccinated family member living there – reminiscent of a public health measure dating back to the Middle Ages, when homes and businesses affected by the black plague were marked.

Vaccination against infectious diseases is one of the great triumphs of medicine. It can be dated back to 1796 when William Jenner, an English country doctor did his now-famous experiment. Country wisdom and his own observations found that milkmaids who suffered from cowpox, a disease that caused blistering on cows’ udders and which caused a mild illness in humans, never developed smallpox. Smallpox was a very serious illness: 30% of those infected died, and many of the survivors were left blind or disfigured. Jenner inserted pus from a cowpox pustule into a cut in eight-year-old James Phipps’ arm and later inoculated James with smallpox and the boy did not get ill. He repeated this with other children, including his own 11-month-old son, with the same results. Vaccination against smallpox was rapidly taken up across Europe.

Vaccines are now available to prevent many once-deadly diseases, including polio, diphtheria, measles, tetanus, yellow fever, typhus and hepatitis. Over the past two decades, with the memory of these diseases fading from our daily consciousness, we have seen the growth of the “anti-vaccine” movement that threatens to undo much of this life-saving progress.

There has always been objection to vaccination. After Jenner’s vaccination became widely adopted, many opponents claimed it was repulsive and ungodly to inoculate someone with material from diseased animals. The widespread awareness of such dread diseases as smallpox overcame these objections, as the vaccine clearly worked, and everyone knew friends, relatives and neighbors who had died. When I was a child, polio was still a dread disease, and the public welcomed first Salk’s and then Sabin’s vaccines. By the late 20th Century, memory of most dreaded childhood diseases had faded, leading people to underestimate the severity of the harms that vaccines prevent.

Much of the current “anti-vax” movement can be traced to a paper by Andrew Wakefield in The Lancet, a British medical journal, in 1998. He and 12 coauthors claimed to have investigated a “consecutive series” of 12 children referred to the Royal Free Hospital with chronic enterocolitis and developmental disorders, including autism, which they linked to MMR vaccination. The General Medical Council of Britain found that the children were carefully selected and that the study was funded by lawyers representing parents suing vaccine manufacturers. In 2010, the editors of The Lancet retracted the paper, apologizing for published a clearly flawed paper, but the damage had been done.

Autism is a serious life-long developmental disorder, whose cause remains unknown. It has a strong genetic component, and even though it may not manifest until early childhood, researchers feel the underlying pathology is present at birth. Parents want an answer, and vaccines provide an easy answer. Multiple studies have been done that strongly repudiate any link between MMR vaccination and autism. Three large studies, in Denmark, the U.S. and Britain have found less autism among vaccinated children than those not vaccinated.

Just as the proliferation of clearly biased news presentations have left all-too-many of us in our own silos politically, those who oppose vaccination can find all the support they want in chat groups and Facebook, science be damned. The problem with letting parents decide is that it is not only their children who are harmed, but the general public. Just as courts have decided that parents cannot let their own beliefs allow them to refuse life-saving medical treatments for their children, parental objections should not allow them to refuse vaccination for their children. A small number of children with immune deficiencies are at risk from vaccines and should be exempt. They will be safe if the large majority of healthy children receive the vaccines, as this makes epidemics very unlikely. Parents who refuse are not “bad” people, but they are seriously misinformed, and should not be allowed to harm others if their minds are closed to evidence.

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Death at an early age

There are many ways to gauge the health of a population, whether a nation or some specific portion of it, but the commonest and broadest measure is the average life expectancy: the number of years a child born will live on average. Life expectancy in developed countries has increased for most of the past century, as antibiotics decreased deaths from infectious diseases and better sanitation became universal. US life expectancy began to lag that of most other developed countries in the late 1980s and by 1998 had fallen to a level below the average among OECD (the Organization for Economic Cooperation and Development) countries. Average life expectancy in those countries has continued to increase every year but stopped increasing in the US in 2010 and since 2014 has fallen, even though we pay almost twice as much per capita as do those countries on health care. Why is this?

Death rates among those 65-84, while obviously high (the biggest risk factor for most diseases is old age!), have fallen substantially between 1999 and 2017, while the death rates for those 25-64 reached a low in 2009 and have risen since. The death rates have risen significantly among those 25-44, as deaths from suicide (usually by gun), opioid overdose and alcohol-related liver disease – diseases of despair - have all jumped. Infant mortality rates have fallen slightly in the US over the past 20 years but remain well above those in other developed countries and are improving at a slower rate than theirs.

Differences in life expectancy are clearly related to factors other than health care expenditure. Researchers have shown dramatic differences in life expectancy among people living in zip codes less than 10 miles apart, sharing access to the same hospitals but having very different household incomes. Increased stress, including economic, has been linked to higher heart attack rates. Rising unemployment or under-employment probably explains the much higher suicide and opioid-related death rates in the industrial heartland, Appalachia and northern New England. Maternal death rates are 5-fold higher among African-American women than whites.

The solution to our discouraging health statistics is not more health care spending. Rather it lies in reining in our excessive and wasteful spending and re-directing this money to such areas as vocational education, improving social support, providing better access to healthy foods and increasing minimum wages. A living wage is the best medicine available for most conditions.

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The problem of rural health care

There are many disparities in health care. Black mothers have a much higher rate of maternal death than do white women. All women are less likely to get guideline-advised cardiac care than do men. Among the many such examples, perhaps the hardest disparity to solve is that of the poorer access to health care faced by rural communities. People living in rural counties have higher death rates from cancer and heart disease than their urban counterparts, and there are more deaths from opioid overdose. Rural hospitals are closing every week, leaving their communities with less local access to needed services. Physicians practicing in rural communities are older and are not being replaced as they retire.

To keep small hospitals open, the federal government created the Critical Access Hospital program in 1997 that pays more to small (25 or fewer beds) and isolated (at least 35 miles from another hospital) hospitals. A friend who is an experienced nurse once told me she thought this was akin to the Chrysler bail-out, and these hospitals provided poor care and should be allowed to close. Many studies have documented poorer processes of care at small hospitals compared to larger one. It is certainly true that small rural hospitals do not provide the same level of service as do larger hospitals. They have few specialists and rarely have anything close to a critical care unit for truly sick patients.

I remember well an experience from many years ago. I was “moon-lighting” in the emergency department of a small isolated hospital when a patient came in with an obvious acute appendicitis that looked about to rupture. Unfortunately, the only surgeon on staff was quite inebriated after a night of partying and clearly in no shape to even drive to the hospital, never mind operate. The weather was foul and getting the patient to another hospital was going to be dangerous, so the nursing staff convinced me, a cardiology fellow, to operate. Luckily the OR nurses knew more about the procedure than I did, and I had assisted on a few appendectomies in medical school, so the patient survived, but at a larger hospital this dilemma would never have arisen.

What can be done? Better transportation would help. In truly isolated areas, air ambulances may be needed. Under our current system these are often exorbitantly expensive and a common source of “surprise medical bills” that run into the $10’s of thousands for non-Medicare patients. State governments and/or referral hospitals should establish fairly-priced air ambulance services if they cannot get commercial providers to bring down their prices. More use of tele-medicine would help, both in providing specialty consultation to the small hospitals and in allowing patients to avoid long drives. It has been found that pre-hospital personnel, EMTs and paramedics, can often avoid taking a patient to the hospital if they have telephone back-up at the scene. Consolidation of rural hospitals to provide more of a critical mass of physicians might require longer drive times but would provide better care in return. Medical schools should recruit more students from small communities, as graduates are much more likely to serve their own or similar communities than are students from an urban background, and rural students are now very under-represented among medical students.

In the meantime, if you are contemplating a move to the bucolic countryside after retirement, look carefully at the medical resources that would be available when you need them!

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Vaping - what we know and what we don't

Some 70 years after Doll and Hill published their landmark paper in the British Medical Journal linking smoking to lung cancer, we know a lot more about both the dangers of cigarettes and the predatory practices of the tobacco industry. A major public health campaign that included both education and regulation has led to decreased smoking and a corresponding drop in coronary disease. We still need on-going efforts, as the effects can be overcome by tobacco advertising. Banning flavored cigarettes or restricting their sale was shown to work in a study comparing youth smoking in Lowell, which had such a restriction beginning in 2016 and Malden, which did not. The consequences of smoking are still a huge problem in China and in many developing countries where tobacco ads dwarf public health measures, so we must stay vigilant.

The new epidemic which requires action is the use of e-cigarettes, or “vaping.” Vaping is the act of inhaling the aerosol produced by a battery-powered device. E-cigarettes contain pre-filled pods of liquids that the user adds to the device, and now are most commonly small devices that resemble a USB stick, and so are easy to carry and use. The liquids generally consist of glycerin, water, propylene glycol, nicotine and flavorings. Juul, by far the leading seller of e-cigarettes, has claimed that they are selling their product as a smoking cessation aid, and prominently feature adult smokers extolling the value of the product for this purpose. However, they clearly market to youth on social media, and by far the biggest selling products are those that are flavored. Flavor was the reason that about a third of users first tried e-cigs and most (63%) current users used flavors other than tobacco. Fruit flavors were most likely to motivate young adults to try vaping. In 2018, two thirds of U.S. middle and high school students had tried e-cigarettes or been exposed to second-hand aerosol in the previous 30 days. E-cigarette use is also a strong gateway to use of tobacco cigarettes among youth, with over 4-fold greater smoking among e-cig users.

Are e-cigarettes safer than combustibles? Clearly smoking causes cancer. Mint- and menthol-flavored e-cigarettes have very high levels of pulegone, a known carcinogen. E-cigarette smoke has also been shown to induce cancerous changes in the lung and bladder of mice. Smoking is a major contributor to coronary disease. What about e-cigarettes? They are associated with an increased risk of myocardial infarction that is similar to that of smoking conventional cigarettes, and dual use is riskier than using either product alone. Many women use e-cigarettes while they are pregnant, perhaps believing that they are safer than combustibles, but e-cig use has been shown to delay implantation and cause reduced weight gain of the fetus. While some short-term studies have shown minor improvements in measures of lung function among COPD patients who switched from combustible to e-cigarettes, vaping has been clearly shown to cause airway inflammation and lung disease. Finally, our dental colleagues have reported that e-cigarette aerosols increase the risk of cavities similarly to gelatinous candies.

Last, but far from least, is the mysterious and frightening epidemic of vaping-related lung disease. This was first reported from the upper Midwest in the spring of this year but has rapidly spread. Vaping-related lung disease has now been reported in 49 states (all but Alaska), DC and the US Virgin Islands. The number of cases is a moving target, but as of Oct 29, 2019, there were 1888 confirmed and probable cases and 37 deaths. The illness consists of early symptoms of nausea, vomiting and abdominal pain, followed by progressive shortness of breath, often leading to respiratory failure and the need for being placed on a ventilator. The chest X-ray shows diffuse infiltrates. The exact cause is still controversial. Among patients with full data, 86% reported use of THC-containing products, 64% nicotine-containing products and 52% both. No single compound has been shown to be the cause. The majority of those affected have been teens and young adults, though the death rate has been higher in middle-aged and older victims. Because the cause remains unknown, the CDC recommends against the use of any vaping products.

The bottom line: vaping is NOT safe, and best avoided.

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What is "pre-illness" and what can you do about it?

OK, so you have been told you have “pre-diabetes” or “pre-hypertension.” What does that really mean? What should you do about it?
“Pre-disease” is a relatively new concept, unheard of when I started practice, but being applied more and more. It simply means that you have some measurement that is abnormal but does not meet the established criteria for a diagnosis. A friend of mine once observed that “there are no healthy people, simply those who have not had enough tests,” and this concept of our fragility seems to be applied more and more. Commonly used labels I have come across, in addition to pre-diabetes and pre-hypertension (now more commonly described as “Stage 1 hypertension”), include dyslipidemia, osteopenia and pre-cancer. The rationale for applying these labels is that catching a disease early, in its “pre-“ stage, and treating it, will somehow help avoid serious problems down the road. The evidence that this is true is very limited.
The CDC recently claimed that 84 million Americans had pre-diabetes – an enormous number, and an enormous potential group of customers for the pharmaceutical industry. An article in the journal Diabetes Care in 2016, however, found that only about 2% of pre-diabetics went on annually to have overt diabetes. At least a third in whom no intervention was carried out reverted to completely normal blood sugars, and the rest remained with mildly elevated sugar values. A more recent study in the same journal looked at 3313 black adults and defined pre-diabetes as a fasting sugar between 100 and 125 (below 100 being normal). They found no increased risk of cardiovascular disease in those with mildly elevated sugars.
Hypertension was previously defined as a BP persistently over 140/90, but values of 130-139/80-89 are now called “Stage 1 hypertension,” and it is estimated that one third of American adults have this “condition.” There are many problems with this labelling. One is that there is increasing evidence that office or clinic BP measurements are not truly representative of our usual BP and are frequently not even measured accurately. Another is that there is to date no evidence that treating this with medication does more good than harm.
Another common “pre-condition” is osteopenia, a bone density below normal but not severe enough to be osteoporosis. Some estimates claim osteopenia affects about 43 million U.S. adults, mostly women. How important is this? A study of 5000 older women with osteopenia found that after 10 years, only 5% had gone on to develop osteoporosis. If you want to estimate your risk of fracture, and you know your actual bone density numbers, you can go to https://www.sheffield.ac.uk/FRAX/ and run the numbers. (If you are a U.S. Caucasian, go to https://www.sheffield.ac.uk/FRAX/tool.aspx?country=9)
What should you do if you have been told you have one of these “pre-diseases.” What I would NOT do is begin medication. You may want to take this as a kick in the rear to motivate you to make some healthy lifestyle changes. Losing a few pounds or beginning a regular exercise program will usually reduce your sugar. Exercise, a more vegetarian diet and cutting down on alcohol will drop your blood pressure. Weight-bearing exercise and a diet rich in Vitamin D and calcium (but not supplements) and stopping smoking will strengthen your bones. Note the common thread in all of these?
Equivocal cancers are a whole other subject, which I will get to in another post.
Happy exercising!

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Should you get a flu shot?

Let’s get one thing out there up front: flu shots are not guaranteed to prevent you getting influenza. Neither are seat belts a guarantee you won’t die in a car crash or bicycle helmets that you will survive getting thrown off your bike, but we still strongly recommend that you wear your seat belt when in a car and a helmet when on your bike. Why? Because they both greatly increase your odds of surviving an accident. It is the same with a flu shot: getting the shot cuts your odds of being hospitalized or dying of influenza by about a half.
A few facts: during the 2018-19 flu season, about 50,000 Americans and 3500 Canadians died of influenza. When the CDC looked patients hospitalized with influenza, those who had received the vaccine had a 36% lower risk of dying and 34% less risk of needing to be on a ventilator than those who had not.
Even if you do catch influenza despite getting the shot, you are going to be less sick and have a much lower risk of passing the disease on to others, which is one reason health care facilities make such a push to get all of their staff immunized.
Let’s clear up some common myths. First, influenza is not just a bad cold. If someone says they missed a couple of days of work because of the flu, they did not have influenza. With influenza you are sick for a good week or more with high fever, terrible cough and ache all over.
Second, you cannot catch anything from the shot. I used to hear “I had a flu shot once and got sick, so now I don’t get one.” The influenza vaccine is a “killed vaccine.” There is no live virus in the shot, just ground up particles from killed viruses. What may happen is that after getting a flu shot you get the same cold you were going to get anyway, and blame it on the shot. While you may get minor soreness at the site of the injection, serious side effects are very rare.
“I’m not around people that much, so I don’t need it.” True if you are a hermit, but not if you are a normal person, even an at-home worker. It is clearly true that school teachers, bus drivers and others who are around lots of people are at higher risk, but in an epidemic year we are all at risk.
Finally, “they never get it right.” We are all aware that some years the vaccine seems more protective than others, because the public health authorities who tell the manufacturers what strains of influenza to include in each year’s vaccine are making “educated guesses,” based on which strains were common in the southern hemisphere during their season. Some years they get it spot on and others they do not, but even a less-than-perfect vaccine is better than none.
So… role up your sleeve and do it before the flu season is in full swing.

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Getting the most from a doctor visit

For most of us, going to the doctor is not at the top of our favorite things to do list, but it may be one of the most important. Whether the visit is for a scheduled check-up or to deal with a new problem, there are ways you can make the visit less stressful and more useful.
You must remember that things have changed. In the “good old days,” when I started in practice, the visit involved just the patient and the doctor. Nowadays, there are many other players, who may not be physically present but are influencing the visit, including insurers, lawyers and the ubiquitous electronic medical record (EMR). I recently saw an article headlined “Don’t let patient care interfere with documentation,” not-so-subtly making the point that doctors are overwhelmed with demands for data to satisfy the demands of multiple third parties; it has been estimated that for every hour directly interacting with patients, doctors spend two hours on administrative tasks. Despite this, most doctors really do want to do what is best for their patients, and you can help them achieve this.
Arrive on time for your visit, but be prepared to wait. Doctors run late for many reasons. It may be the fault of the office, scheduling patients to maximize the doctor’s time at the expense of patient convenience, and if you ALWAYS wait a long time, you may want to change doctors. More common reasons are that earlier patients arrived late but were seen anyway or that patients had more complicated problems than anticipated, turning a 15-minute visit into 30 minutes or more.
Silence or turn off your cell phone! It is hard enough to have a good conversation about an illness without the distraction of a phone going off. If you actually answer the phone, my reaction would be that since you are clearly not very worried about your health problem, I will not be either.
Do your homework and arrive prepared. While the doctor may be the expert on medicine, you are the expert on your own body, and you are the one to note that while a symptom may not be dramatic, it is new. Before the visit, put things down in chronologic order – what happened first, what happened next, and over roughly what time frame. It is OK to check your symptoms “on-line,” but please use a legitimate web site such as NLM.gov, CDC.gov, webmd.com or mayoclinic.org and do not “google” your symptoms. Whatever you do, do not say “I read on Facebook…” or your doctor will mentally tune out everything else you say.
Bring notes and take notes. It is easy to get side-tracked and forget things you thought were important. Have a summary of prior surgery, current medications, medication allergies and major medical problems printed and on your phone. Since it has been shown that 80%+ of what a doctor says is forgotten by the time you leave the building, either bring a friend or family member to act as a scribe and second pair of ears or make some written notes. Ask the doctor if it is OK to record the visit so you can listen to the conversation and advice given when you are less stressed.
It is OK to question the doctor. While doctors know a lot more about medicine than you do, we are not infallible. If the doctor dismisses a complaint when you “know” something is wrong, it is reasonable to ask for a second opinion. Misdiagnosis is increasingly recognized as a serious problem. You should be prepared to ask the doctor why they have made a diagnosis and what else it could be. You should also have a timetable for when you should feel better and what the plan is if you do not respond to the suggested treatment.
Remember: it is not your job to please the doctor; it is the doctor’s job to help you feel better. If you have a doctor with whom you cannot communicate, look for another.

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Where's the beef?

A study published by the Annals of Internal Medicine on October 1 titled “Unprocessed Red Meat and Processed Meat Consumption: Dietary Guideline Recommendations from the NutriRECS Consortium” has unleashed a firestorm of controversy. This publication and the reaction to it reveal so much about medical studies and recommendations that I was tempted to write a book about it, but will try to be briefer.

The conclusion of the paper was that adults continue their current consumption of both red meat and processed meat, noting that the recommendation was a weak one based on low-quality evidence. The reaction from such groups as the Harvard School of Public Health, the American Cancer Society and the American College of Cardiology was vehement opposition to this statement, implying that the authors were irresponsible and would contribute to more heart attacks and cancer.

Why the controversy? First, we must note that the ideal way medical recommendations are reached is through randomized controlled clinical trials: a group of people are given treatment A or Treatment B, selected randomly, and neither the subjects nor the researchers know which they get. The groups are followed for an appropriate time and at the end, the researchers look for a difference in the outcome between those given A and those given B. If there is a substantial difference between the groups, and if the people given A and those given B are shown to be pretty much the same except for the treatment, it is assumed that the difference in outcome was due to the treatment. I must note that small differences in outcome may be “statistically significant” if the groups are large enough even though the magnitude of the effect may be so small that it is not “clinically significant.”

While randomized trials work well when comparing two medicines, they are impossible to do when studying diet. Most of us can tell the difference between a steak and a roasted cauliflower. Dietary studies are thus mostly done by looking at what people do, generally based on self-reporting, and comparing the outcomes between those who claim to eat one way or another. These observational studies are fraught with difficulty. We learned long ago that when you compare people who do one thing differently, it is highly likely they do other things differently. Studies comparing vegetarians with omnivores cannot assume that their diets are the only thing different between them. Vegetarians may smoke less, may drink less (or more), may exercise more, may be leaner – all factors that impact health.

The NutriRECS group took this into account when they looked at all the published studies on diet and health. They concluded that the evidence base for recommending people cut down on their consumption of red and processed meat was weak. They also noted that the absolute benefit, in terms of number of heart attacks or cancers prevented, was relatively small. One example was an estimated 7 fewer cancers per 1000 people over their lifetime, a risk that omnivores might be willing to take when weighed against quality of life.

So, who is right? Both sides! If you are a vegetarian, you can be satisfied that you are slightly reducing your risk of cancer and heart attack (though slightly increasing your risk of stroke per another recent study in the British Medical Journal!) If you like to eat meat, you can be content that the absolute risk of your preference is relatively small and you do not need to make yourself miserable – and you can always balance your love of steak by walking more and dropping a few pounds.

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The computer will see you now

I recently saw a cartoonist’s view of where the clinical encounter is going. A new doctor was being shown an exam room with a doctor and a nurse standing by a computer and was told “The computer will diagnose the patient and prescribe treatment.” But, the new doctor asked, what does the doctor do? “Oh, the doctor reads what the computer said to the patient.” And the nurse? “The nurse slaps the doctor’s hand if they deviate from what the computer says.” With all the recent hype about Artificial Intelligence (AI) and Big Data, is this truly the future of medicine?

In the traditional medical encounter the patient describes their story and the doctor asks questions to expand and clarify the symptoms, followed by a physical exam: the classic H&P (History and Physical) that have been little changed for millennia. A paper in the British Medical Journal back in the 70’s found that about 75% of diagnoses were made on the basis of the history, with the physical exam taking this up over 80%. Less than 20% of diagnoses needed lab tests or X-rays, though these helped confirm the H&P.

The future, we are often told, involves computers crunching the numbers on millions of patients and finding previously unknown connections and making better diagnoses and better prognostication that doctors have been able to do. Most of the big tech companies, Apple, Google, Amazon, IBM, as well as numerous start-ups, are betting billions of dollars on the future role of AI in medicine. Successes to date have been limited but well-touted. The areas which seem most promising involve very specific well-defined tasks where there is good data for the computers to crunch and where the answer is clear-cut. Examples include evaluation of skin lesions to pick out melanomas, diagnosis of retinal lesions from retinal photographs and specific questions in radiology. When such AI systems look at less well-defined problems, the successes to date are not evident.

When looking at people with ill-defined complaints, the medical record contains a lot of “noise:” data that may be relevant or utterly irrelevant to their problem. To date, physicians seem much better at separating the wheat from the chaff than do algorithms. There is another factor at play: association is not the same as cause and effect. The classic example is the old finding that when an American League team won the world series, the stock market went up. While this is interesting, I would not want to bet my retirement on this investment advice. Similarly, if computers look at large data samples, there will invariably be associations found purely by chance if enough data is crunched. Humans are needed to ask if this is plausible, if there is some possible biologic basis for the association. Another monkey wrench has been thrown into the mix: a study compared what emergency medicine residents documented in the electronic record and what they were observed to do by researchers who shadowed them. A claim of AI evangelists is that now that so much data is available via the EMR that was previously locked away in doctors’ scribbled handwritten notes, new insights are ready for the analysis. The study found that when the observers’ records were compared to the data in the EMR, there was a match for only 38% of medical history items and 53% for the physical exam. It is so easy with EMRs to click and document something you never did that notes are invariably bloated – after all, a longer note justifies a higher bill. Crunching invalid data is unlikely to result in valid conclusions!

There is also the fact that physicians are to a degree confidants and counselors as well as technicians. Your genome may suggest what diseases you are prone to get, but a human who knows you can put that in context and suggest what things you as a unique individual should do.

With all our high-tech tools, the old-fashioned H&P was recently shown to still have value. A study in Circulation found that despite the availability of echocardiograms and bio-markers, physical exam findings in patients with congestive heart failure offered significant independent prognostic information.

Bottom line? A physician using current and developing AI tools will often do a better job, but AI is not yet ready to replace the human.

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New but necessarily improved

One of the major arguments that Big Pharma and its apologists make against any attempt to lower the sky-high prices Americans pay for medication is that doing so would stifle innovation. While it is true that many new drugs introduced in recent years have helped extend life, it is also true that many have been of marginal benefit at best. One example is the recent flurry of “check-point inhibitors” that have been tested against a variety of cancers. There are now six checkpoint inhibitors on the market and more on the way. The Cancer Research Institute estimated recently that some 2,250 clinical trials are underway testing this class of drugs. Unfortunately, many of these trials duplicate each other, and three recent studies looked at the use of these drugs against multiple myeloma. All three showed no benefit. Did we really need to put so many patients through these trials? Could not the investigators have waited for preliminary results from one before starting another trial?
Many cancer drugs are approved by the FDA based on “statistically significant” improvement in life span even if the extension is measured in weeks and comes at the price of nasty side effects. Still others are approved based on so-called “surrogate end-points:” tumor shrinkage or lab test improvement, even if they have not shown any improvement in lifespan. We really need pharmaceutical companies to be looking for drugs that give meaningful extension of life without horrid side effects rather than developing yet another “me-too” drug that will probably be able to obtain FDA approval and then be marketed at high price.
Another way drugs can get FDA approval without offering much benefit is by showing “non-inferiority” compared to a treatment already approved. Do patients really want to be offered a drug that “is probably not much worse” than another? A recent study published in JAMA Network Open at the end of August 2019 looked at 74 such trials of cancer drugs. While 61% could justify their use by offering convenience (such as oral rather than IV use) along with similar survival, 39% offered no obvious reason to choose the new drug over an old one - but did come at higher cost. The majority of trials showing non-inferiority without any justification for caring if the new drug was probably as good were industry-sponsored.
To regain our trust, the pharmaceutical companies need to show they are concentrating on developing truly innovative drugs that make a difference in patients’ lives and not just pushing out high-priced drugs that do little to improve quality or quantity of life but do add to our already staggering financial burden.

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Less may be more

Homeopathy is a medical system based on the belief that the body can cure itself. Those who practice it use tiny amounts of natural substances, like plants and minerals. They believe these stimulate the healing process. While homeopathy has never caught on as well in America as it has in Europe, there is something to be said for “less.”
Most Americans have always equated “more” with “better,” but several recent studies have pointed to the fallacy of this belief. We need iron to build hemoglobin as well as many other functions of the body, but too much iron is toxic. Our bodies have thus cleverly built in a mechanism to protect us from excessive iron. A protein made in the liver, hepcidin, stops iron absorption when too much iron is sensed. We were taught in medical school to treat iron deficiency anemia with as much oral iron as the patient could tolerate (excessive iron causes a lot of stomach distress). Well, it turns out that by upping the dose of oral iron simply turns on the hepcidin and blocks iron absorption. The optimal dose of iron to treat patients with iron deficiency is not the traditional 300 mg/day, but 200 mg every other day!
Vitamin D gives another example. We need Vitamin D for strong bones; it is needed for our bodies to absorb calcium. Since the main sources of Vitamin D are sunshine acting on our skin to let us produce our own Vitamin D or milk fortified with Vitamin D, many adults are deficient in this crucial vitamin, particularly those living in Northern climates, where for much of the year there is not enough sun exposure for us to manufacture our own. Deficiency of Vitamin D leads to osteoporosis and falls, with resulting fractures. National guidelines recommend that adults take 600-800 Units of D daily. Well, if 600 is good, more must be better, right? If you go to your pharmacy, you will see Vitamin D capsules of 1000, 2000, and even 5000 Units. Unfortunately, studies have shown that older adults who took 4000 Units daily had slower reaction times than those who took the recommended 800 U and were more likely to fall. A more recent study has shown that those taking 5000 U or more paradoxically had more fractures than those taking lower doses. High doses of Vitamin D can lead to excess calcium absorption, with high blood levels, and this in turn can cause nausea, constipation and excess urination or even kidney failure.
So, take the recommended dose, but do not think that doubling it up will be better!

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To vape or not to vape...

What is an e-cigarette and why should you care? Electronic cigarettes are battery-operated devices that heat a liquid solution to generate an aerosol that users inhale. The liquid contains nicotine and a liquefier, either glycerin or propylene glycol, and flavoring. While the device itself can be as large as the pipe smoked by Sherlock Holmes or a cigar, most are closer to the size of a cigarette. The most popular delivery device is smaller than a standard disk-on-key and sold by Juul.
Juul is heavily marketing their product as a healthier alternative to cigarettes and claims to be marketing only to adult smokers. For those of us with long memories, this recalls filtered cigarettes being marketed as a healthier choice, or the “doctors prefer Camels” ads of even longer ago. The fact is that use of e-cigarettes by U.S. youth surpassed their use of traditional cigarettes in 2014, and by 2017, 20% of high school students reported having used them. Studies have shown that among teens and young adults who have not previously smoked, the odds of starting are three to six times greater among those who have tried e-cigarettes. A study published on-line this week on JAMA NETWORK found that the odds of marijuana use in adolescents and young adults was 3.5 times higher among those who used e-cigarettes.
Are there any health benefits? Switching from cigarettes to e-cigarettes does reduce the amount of tars and other carcinogens inhaled. Among smokers with chronic lung disease who switched, there were fewer reported lung symptoms (cough and shortness of breath), and measured lung function improved slightly in those who switched.
The harms are led by the fact that e-cigarettes deliver nicotine, a highly addictive substance and one which damages brain development in youth, and that they appear to act as a “gateway” to use of traditional cigarettes and marijuana. The delivery of nicotine is highly variable, and nicotine poisoning can occur. There are many unknowns about the effects of the liquids inhaled.
More dramatic ill effects have led headlines. There have been at least two cases reported in which the lithium batteries led the device to explode, in one case killing the user by severing his carotid artery (the main artery in the neck bringing blood to the brain), and in another shattering his jaw and requiring multiple surgeries to correct the damage. These may have been flukes, but there is a reason that airlines do not let you pack lithium batteries in checked baggage. Between 2009 and 2016, the US Fire Administration recorded 195 documented incidents of fire and explosions involving e-cigarettes, resulting in 133 injuries, 38 severe enough to require hospitalization.
The FDA announced on August 20 that it had received 127 reports of seizures or other neurological symptoms suspected to be related to e-cigarettes over the period 2010-2019. In addition to seizures, some people suffered fainting or tremors.
Also very worrisome are the reports from several states this summer about a mysterious severe lung disease among previously well adolescents and young adults who vaped. First reported in Wisconsin, multiple cases have now been reported from Illinois, California, Indiana and Minnesota. The CDC has at least 94 cases from 14 states reported between June 28 and August 15, 2019 under investigation. These previously healthy young people developed cough and shortness of breath, and some required respirator support. No infectious cause could be found. While a cause-and-effect with vaping cannot be proven, it was the common thread.
A recently published study in Radiology reported that inhaling even nicotine-free e-cigarette vapor in healthy young non-smokers caused constriction of blood vessels.
The bottom line? If you are not now a smoker, do not try these thinking they are “safe.” If you are a smoker who has been unable to quit, switching to e-cigarettes MAY be slightly less unhealthy, with a lot of unknowns. All of us should work hard in our communities to keep e-cigarettes out of the hands of youth and make education about their harmful effects part of the school curriculum.

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Low value care

Doctors and policy wonks hear a lot these days about “low value care.” What exactly is that, and should you care? The term refers to tests, medications and procedures that add little to a patient’s health or well-being but which cost them or the system more money than any benefit warranted. Some of the earliest research that looked at this was done at Dartmouth, where they found enormous variations in the cost of treating various conditions in different parts of the country with no correlation with outcomes. In my own practice, I remember seeing a long-time patient who had become a snow bird. When he returned north and came to see me, he told me that he decided to hook up with a local doctor should he get sick while in Florida. The doctor did not have any available appointments, but it was suggested he come in and get an ECG and blood tests before the visit (inappropriate for an unknown patient!), which he did. The next day he got a call: his ECG was abnormal, showing he had had a heart attack, and so additional tests were scheduled. An echocardiogram and stress test were done, followed by a catheterization – all of which were normal. Fortunately, he suffered no adverse consequences beyond some anxiety, but this whole sequence, starting with a “routine” ECG, epitomized low value care.
Numerous examples abound. Complex imaging such as MRIs and CT scans for non-specific back pain rarely lead to any change in therapy and often find red herrings. Most of us over 60 have some abnormality on a back image, even those who have never had a backache in their life, and these may lead to totally inappropriate surgical procedures. Tests for various rheumatologic disorders, such as ANA (anti-nuclear antibody, a screening test for lupus) and Rheumatoid factor, elevated in rheumatoid arthritis, are often positive in healthy elderly people. When these tests are ordered for people who have osteoarthritis, the meaningless positive test may lead to unhelpful and even dangerous treatments for a disease they do not have. PSA testing in men well over 75 may discover low grade prostate cancers that would not have bothered them if never discovered but which lead to treatments with serious and life-long side effects, lowering their quality of life. Other tests, such as imaging for plantar fasciitis or CT scanning for uncomplicated sinusitis do little harm but are costly and add nothing to change in therapy.
The difference between settings and individual doctors are remarkably large, with the use of studied low value services varying as much as 8-fold. Researchers have been unable to find any obvious characteristics that differ between those who order a huge number of such tests and procedures and those who do not: neither age, gender nor medical school seem to affect this behavior. The solution lies in both continuing education of the doctors and perhaps in harnessing the electronic record to request that certain orders be justified before proceeding. Patients, too, should play a role, and not request tests that the doctor feels are not needed after some discussion about the usefulness of the test. There have been various attempts to estimate how much of our bloated health care expenses represent waste, but a growing consensus is that 20-25% of what we spend goes for low value care. To get a handle on costs, this would seem to be the “low hanging fruit.”

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When, oh when, will it end?

The National Rifle Association recently condemned doctors who are against gun violence, telling us to "stay in our lane." Reducing preventable deaths is the main lane for doctors.

And despite thinking that doctors would not be targeted because we are here to help, we are not immune. The tragic shooting at Mercy Hospital in Chicago on November 19 that left an emergency physician among the victims brought home to physicians how vulnerable we all are to acts of violence.

The Centers for Disease Control and Prevention released last fall a report on firearm homicides and suicides. In an understated way, it said that “firearm homicides and suicides represent a continuing public health concern in the United States.” In 2015 and 2016, the U.S. experienced 27,394 homicides, including 3,224 among youths ages 10 to 19, from guns. In the same period there were 44,955 firearm suicides, including 2,118 among 10-to-19-year-olds.

We are so much worse than any other Western democracy that comparisons are almost meaningless. As I point out in my book, Prescription for Bankruptcy, people can attempt suicide by many means, but none are nearly as “successful” as suicide by gun. Most people who attempt to kill themselves by cutting their wrists or taking an overdose survive, and repeat attempts are rare. The fatality rate when the means used is a firearm is close to 100%.

Last May, CNN reviewed data on school shootings around the world. While this study was less than truly scientific because it relied on media reports and, thus, might have missed shootings in which no one died, what it found was sad enough. From January 1, 2009 through May 21, 2018, there were 288 shootings with fatalities at U.S. schools, including grade schools and colleges and universities. This was 57 times as many as in the rest of the G7 nations combined. There were two school shootings each in France and Canada, one in Germany and none in Japan, Italy, or the United Kingdom.

A study in Health Affairs last January looked at the death rates among children and teenagers in 19 countries in the Organization for Economic Cooperation and Development. Teens in the U.S. were 82 times more likely to die at the hand of a gunman than were their peers in the other 15 countries.

We are well aware of what happens after each mass slaughter of innocent people. Politicians mouth platitudes and offer their prayers and comfort to the victims and their families. They then hop back in the pockets of the NRA and do nothing to prevent the next shooting. Will this time be any different? Not unless we rise up and DEMAND action or loss of their seat in Congress.

We can lower firearm fatalities without infringing on the legitimate use of firearms by hunters. Massachusetts has one of the toughest gun laws in the nation and the lowest death rate from firearms. If every state in the country had a similar law and death rate from guns, tens of thousands of American lives could be saved.

To own a gun in Massachusetts, you must obtain a permit from your local police department. This requires paperwork, an interview and a background check. In addition, the local police chief may use discretion if he or she knows something about you that does not show up in your criminal record. Only after you get this permit can you go to a gun store and purchase a firearm. All firearms are registered, and if you get yours from a relative or private seller, that person must verify that you have a permit. Certain weapons, such as automatic weapons and sawed-off shotguns, are illegal. Firearms must be stored in a safe or with a trigger guard. While 97% of permit requests are granted, it is assumed that many people do not bother requesting one knowing the process.

A clear majority of Americans want better gun control. Allowing hunters and others with a legitimate need to own rifles or shotguns after background checks would respect their rights while protecting our right to live. We must stand up to the NRA and tell our elected officials they will not be re-elected if they do not grow spines.

Physicians, dedicated to preserving lives, must take a lead, acting both as individuals and working through their organizations in fighting for common sense gun laws and making it clear that this is as high a priority as fighting the opioid epidemic to avoid senseless preventable deaths.

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Medical myths and reality

One of the few things I remember from my medical school 2nd year pharmacology lectures was the maxim: “When a new wonder drug comes out, use it immediately, because in a year it will not work as well.” This tongue-in-cheek witticism expressed very well the notion that many of the things that doctors do are as much based on hope and limited data as on solid evidence.
There has been a lot written in recent years about low-value care: medications, tests and procedures that offer little benefit at all or which offer no more benefit than a less expensive alternative. A program started by the American Board of Internal Medicine Foundation called Choosing Wisely attempted to identify low value care by polling specialty organizations for recommendations in their fields, but as I point out in Prescription for Bankruptcy, this got the expected result. The procedures that the organizations suggested should be stopped were for the most part procedures rarely done or done by someone other than the organizations’ members.
A recent careful review of randomized trials published in three prestigious medical journals found almost four hundred “reversals:” findings that countered conventional wisdom and current practices. Examples abound. Many patients with Alzheimer’s disease appear depressed, and it seemed logical to treat them with standard antidepressants that work for non-demented patients, but a large trial found no benefit in the Alzheimer’s population. The American Cancer Society has recommended that women 40-49 get a mammogram every 1-2 years but a very large study found no benefit. When patients are admitted to hospital with congestive heart failure, catheters are still often inserted into the pulmonary artery to measure pressures and guide therapy even though trials going back 15 years found that use of these catheters increased complication rates and had no decreased mortality benefit. Lumbar spinal stenosis is a common cause of back pain, particularly in older patients. When severe, surgery can help, but for most patients, steroid injections are recommended despite a trial published five years ago showing no help of these injections. When an athlete suffers a torn meniscus in the knee, they are usually offered arthroscopic surgery as the quickest way back to full activity. This procedure is also widely used for the much commoner situation of a middle-aged or older patient with osteoarthritis and a torn meniscus on MRI even though a careful trial found no benefit of arthroscopy over physical therapy.
[Those who want the full details are directed to https://doi.org/10.7554/eLife.45183]
To get the best care at a reasonable cost, we need to rely more on science and less on “that’s what I do.”

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Shop 'til the prices drop

It has been said, only partly in jest, that only five people in the world understand U.S. drug pricing, and that they all work for pharmacy benefit managers (PBMs). Readers of Prescription for Bankruptcy or of these postings know that I feel that the entire pharmaceutical enterprise in this country is dedicated to maximizing profit, patients be damned. Recent studies have only reinforced this belief. Earlier this month, drug pricing research firm 46brooklyn analyzed pricing of generic drugs and found unbelievable variation. As an example, Medicare Part D sponsors priced a generic antipsychotic drug aripiprazole (brand name Abilify) from less than 30 cents a pill to over $22 a pill. Generic drugs have a true market-based cost. This is the ingredient cost plus a reasonable margin to keep the PBMs and pharmacies in business. This cost is easily found in pricing benchmarks such as the National Average Drug Acquisition Cost, which is published on-line. This price can then be compared to the better-known Average Wholesale Price (AWP). Most insurers pay some discount to the AWP, and if they are getting a sizable discount, assume this is a good deal. The disconnect between these two prices can be enormous. 46brooklyn Research gave an illustrative example. The median NADAC price for extended release duloxetine (generic Cymbalta) has fallen from $6/pill to pennies. The AWP has stayed rock-steady at $8/pill. So much for generics automatically saving money!
Earlier this summer, MASSPIRG looked at prescription drug pricing at over 250 retail pharmacies across 11 states. They compared the cost to a patient for 12 commonly-used medications, including thyroid, branded and generic Lipitor, Lantus insulin and others. The MASSPIRG staff and volunteers called the pharmacies and asked for the cash price for a typical 30-day supply. The range of prices was, to say the least, broad. 30 tablets of 10 mg lisinopril, used for blood pressure, could cost you from $3.99 to $59.02. 30 tablets of 40 mg atorvastatin, used to lower cholesterol, ranged from $6.99 to $393. 30 tablets of branded Nexium ranged from $54.94 to $950.45; the generic version, esomeprazole, from $10 to $338.40. We have all heard the horror stories of diabetics getting sick and even dying because they could not afford their insulin. Five pens of Lantus insulin ranged from $96 to a chilling $1,759.19!
What is the take-home? First, we must hold our legislators’ feet to the fire and get the industry to start putting patients at least on a par with profits. There is no reason pharmaceutical companies cannot earn a profit, nor are pharmacies charitable organizations, but some limits must be set. As individuals, do what I have always advised my patients – let your fingers do the walking. If you are paying more than $20/month for a prescription, call around. The MASSPIRG staff found that independent pharmacies often had lower prices than did the big chains, so be sure to include some of them in your search. Your wallet will be happier.

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How to prep

You know you should have a colonoscopy, right? Katie Couric says so. Your doctor says so. The US Public Health Service says so. Why haven’t you? The procedure itself is usually a piece of cake – you are sedated and the procedure is over before you know it. Colonoscopy is one of the few screening tests about which there is very little disagreement of its value.
One problem, unfortunately, in our crazy quilt “system” is cost. If your insurance does not cover it, the procedure will cost you thousands of dollars. If you have a high-deductible plan, the cost may run up to your deductible.
For everyone, regardless of insurance, however, the major factor that leads many to refuse the test is the dreaded “prep.” For the gastroenterologist to perform the test properly, you must have a clean colon. If there is a lot of fecal material still in the bowel, they may not be able to do the test at all, or they may do it but not be confident they have seen what they need to see. The standard way of achieving a clean colon has been to require you to drink a gallon of a foul-tasting liquid called GoLytely the day ahead. Most of my patients who did this once said they did not mind the colonoscopy itself, but that there must be a better way to a clean colon.
It turns out that there is. Many colonoscopists have begun using MiraLAX in Gatorade along with bisacodyl tablets in place of GoLytely. The taste is much better – you really only taste the Gatorade – and the volume to be drunk less. Instead of a gallon, the volume is halved – two quarts. This prep was tested in a trial in Boston and found to be as effective as the old standard and tested again at a community hospital in Michigan. In the latter study, about 400 patients who took MiraLAX/Gatorade were compared to a similar number using GoLytely. In both groups, about 90% had an excellent or good bowel cleansing. There is no getting around having diarrhea – no diarrhea, no cleansing – but with the new prep, the taste is clearly better.
So, as the commercials say: ask your doctor if is this right for you.


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Do I really need those vitamins?

Americans love their vitamins and “nutritional supplements.” Surveys have shown that over half of us take at least one and 10% use at least 4 dietary supplements daily. Among those 60 or older, use is even higher; 70% take at least one and 29% take four or more supplements. The market is huge, in the billions of dollars, and “brand extension” is common. You can buy multivitamins, multivitamins for women and multivitamins for seniors. Vitamin D capsules crowd the shelves with sizes from 1000 units to 4000 units and more. Ever since chemist Linus Pauling pronounced it a miracle, millions of us use Vitamin C to prevent or cure a cold.
Besides making money for the manufacturers, pharmacies and GNC, do vitamins and supplements do any good? Clearly it is important to replace any deficiencies. If you have pernicious anemia, (https://www.whatswrongwithhealthcareinamerica.com/2019/06/b12-deficiency-great-imitator.html ) you need Vitamin B12, either by injection or in very large doses by mouth. If you do not drink milk and avoid the sun, you may well need to take Vitamin D. If you are a woman with very heavy periods, a daily iron supplement may be needed. Certain vitamins have been shown helpful in slowing the advance of macular degeneration.
What about the vast majority of supplement users? Most people who take these products take a multivitamin, but rarely is that the only product used. Other commonly used supplements are omega-3 or fish oil, calcium, Vitamin D, Vitamin C and botanical products. Ironically, but not surprisingly, supplement users are much more likely than non-users to say that they try to eat a balanced diet, see their doctor regularly, get a good night’s sleep, exercise regularly and maintain a healthy weight. Many studies over the years have looked at the benefits of taking various forms, particularly at their effect on cardiovascular disease, still the number one killer in western countries.
A recent study published in the Annals of Internal Medicine looked at 277 trials involving 24 supplements or combinations of supplements and almost 1 million subjects. These studies found that reduced salt intake lowered the death rate in all and cardiovascular death in subjects with hypertension. Omega-3 long-chain polyunsaturated fatty acid (LC-PUFA) reduced the risk of coronary disease and heart attacks by a modest amount (7-8%). Use of folic acid was associated with a 20% decreased rate of stroke. Somewhat alarmingly, use of calcium plus Vitamin D was associated with a 17% increased risk of stroke. All the other supplements, including Vitamins B6 and A, multivitamins, “antioxidants” and iron had no measurable benefit. Some 25% of us over 50 take a supplement touted as good for "brain health," but the AARP Global Council on Brain Health has come down strongly against this practice, calling it a "massive waste of money."
Bottom line? Don’t waste your money. If you eat a balanced diet, the odds are you are getting all the nutrition you need. If you feel better taking a multivitamin, there is no evidence it does you any harm, but you are better off choosing the house brand and saving money. If you are shoveling down 8 or 10 “supplements” daily, you are probably wasting your time and money.

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Is dementia the price to pay to be dry?

First, a little background and terminology. Our brain cells talk to each other via “neurotransmitters.” One of these is a compound called acetylcholine. There are two relevant classes of medication that act on acetylcholine. One group are anticholinergic drugs, which block the effect of acetylcholine. These are used in many ways, and there are many subgroups. They are used to treat vertigo and nausea; they are used to prevent seizures; they include many of the older antidepressants, antipsychotics and antihistamines; they are antispasmodics for the intestine, and notably, they are used to treat urinary incontinence. The other class of drugs are cholinesterase inhibitors. The chemists among you will figure out that these block the breakdown of acetylcholine and so increase its effect. The best-known of this class are the drugs used to slow the progression of Alzheimer’s Disease.
It has been long-known that use of anticholinergics can cause confusion in elderly patients, and doctors have been taught to use these cautiously. What has not been known is if they have any long-term effect in patients who seem to tolerate their use. A study published online in JAMA Internal Medicine in June looked at this by studying a very large (30 million patients) British research database. They compared patients diagnosed with dementia with those who were not, matched by age and gender. They then looked at use of any of over 50 drugs with anticholinergic properties by type and by duration of use. They found that patients with dementia were much more likely to have been prescribed an anticholinergic drug over extended periods than were controls. The drugs that most clearly showed this effect were from the group that were expected to be used daily for a long time.
I would like to call your attention in particular to the group of drugs used to treat urinary incontinence. I do this because they are very widely advertised and widely-used by middle-aged and older women. They tend to be used for indefinite periods. They are also of marginal benefit at best. Many of the other drugs in this class are of less current concern because they are used only infrequently (anti-nausea, muscle relaxants) or because they have been largely replaced by newer drugs (tricyclic anti-depressants). Bladder problems are very common and while not life-threatening can be annoying and embarrassing. Oxybutinin (Detrol and other brands) is probably the most widely-used drug to treat overactive bladder. It universally causes a dry mouth, such that the increased thirst works against the desire to void less often.
While this was an “observational study,” and not a randomized trial, it has some inherent validity. We know that anticholinergics can cause confusion in some users. We know that acetylcholine is important in brain function. We know that drugs that increase acetylcholine have some benefit in dementia. My advice is to use these drugs only if other remedies have failed and only if the benefit is very strong. If your reaction is “well, it seems better than nothing,” I’d think twice. Maybe a pantie-liner would do as well and be safer.

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Better than roses?

On June 21, the FDA approved for marketing bremelatonide (trade name Vyleesi) to treat acquired generalized hypoactive sexual desire disorder (HSDD) in premenopausal women.
While I expect push-back commenting on this topic as a male, I am also a physician, and I think this represents a flaw in our drug-approval process. HSDD is defined in the psychiatrists’ “bible” of DSM (The Diagnostic and Statistical Manual of Mental Disorders is the handbook used by health care professionals in the United States and much of the world as the authoritative guide to the diagnosis of mental disorders) as low sexual desire that causes marked distress and/or interpersonal difficulty and which is not due to a co-existing medical or psychiatric condition. It can be diagnosed in both men and women, though I am unaware of any products marketed or in development to increase male sexual desire. Vyleesi is not the first medication for improving women’s sexual desires. Addyi, a drug approved by the FDA in 2015, also improves women’s sexual desires by working kind of like an anti-depressant. However, earlier this year, the FDA issued new safety orders mandating that the drug’s labeling include a boxed warning — the agency's strongest warning — after reports of concerning side effects, including severely low blood pressure and fainting, especially when used with alcohol. Many women’s groups were and remain unhappy that Addyi was approved as quickly as happened.
Changes in sexual desire are natural and may come and go depending on personal events or partner-related issues. When the lack of interest in sexual activity lasts longer than six months and causes distress, however, the criteria for a sexual desire disorder may be met. There are many reasons other than a “medical disorder” such as HSDD to cause decreased interest in sex. These may include, in part, negative attitudes about sex, relationship difficulties (poor communication, abuse), stresses such as financial difficulties, job loss, bereavement, etc., history of emotional or physical abuse, alcohol use, worry about children wandering in or simply a partner’s poor hygiene.
Leaving this all aside, how wonderful is Vyleesi? Is it a “cure?” The drug was approved based on two trials that compared the active drug in different doses versus placebo. The drug must be injected under the skin of the abdomen or thigh at least 45 minutes before anticipated sexual activity (so much for spontaneity!). Possibly showing the power of placebos, the trials found that 25% of women using active medication had an increase in their sexual desire scores, compared to 17% of those using placebo. 35% of women who used the drug had a decrease in their distress score versus 31% of those using placebo. While the manufacturer will tout the “47% greater improvement” experienced by women using the active drug (17% increased to 25%), I think a more realistic viewpoint is that the drug benefitted 8 out of 100 women who used it.
What about side effects? About 40% of the women in clinical trials experienced nausea, and in 13% the nausea was severe enough to require medication. It also caused a transient (up to 12 hours) increase in blood pressure, meaning it should not be used in women with high blood pressure or cardiovascular disease. The drug will go on sale in September, and a price has not yet been announced.
Worth it? You can decide for yourself, but I’d try roses first.

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Be nosy - read about yourself

For centuries, doctors felt that their notes were their property, and none of the patients’ business. This attitude slowly shifted, and the Health Insurance Portability and Availability Act (HIPAA) of 1996 put into law the fact that patients must be allowed to review and get copies of their medical records. Despite this, access to records has remained a daunting task for many. A study done in 2017 of 83 hospitals, all “top ranked” by US News and World Report, found that the information patients were given by phone often differed from that on the forms they had to sign, and that a majority of hospitals charged well over the federally-suggested cost for an electronic copy. Many refused to supply records in the format patients requested, even though this is mandated by law.
Is it worth the bother? Increasing evidence says that you should read your own medical records. There are many benefits. A common failing of current Electronic Medical Records (EMRs) is that they are filled with cut-and-paste from prior notes and often propagate misinformation. An old note says you had an appendectomy as a child and this is carried forward indefinitely, even if you still possess your appendix. Ditto for medicines you stopped taking eons ago, and allergies you never had. If for no other reason, it is worth looking through your record for such mistakes and having them corrected.
Beyond correcting errors, there are many benefits to reading your own records. Some seven years ago, researchers looked at how both doctors and patients reacted to completely “open notes.” Patients at three primary care practices, in Massachusetts, Pennsylvania and Washington State, were given complete access to their doctors’ notes via a secure portal. Included were 105 PCPs and 13,564 of their patients. 11,155 patients opened at least one note, and almost half of these completed a survey on their reactions. Over 80% reported that open notes helped them feel more in control of their care and three quarters of those taking prescription medications said that they were more regular with taking these after reading about their condition. About a third said they shared the notes with others. On the down side, a third had privacy concerns, worrying that others might get into the records and about 5% found something in the notes that was worrisome or offensive. At the end of the experiment, 99% of the patients wanted open notes to continue. The doctors were initially hesitant, but only rarely did the practice result in longer visits or more time addressing issues outside of visits, and none opted to stop when the experiment ended.
One of the biggest problems in patient-physician interactions is that patients find it hard to process all the information they are given during a visit, and it has been repeatedly shown that much of what a doctor says is quickly forgotten. I have advised people to take notes during visits and/or to bring a friend or relative with them as a second pair of ears. Having the ability to read and reread notes of the visit is another good way to be sure you truly know what happened at the visit.
Be an “engaged” patient. Read those notes.

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News you can use

Several studies reported this week in medical journals had useful findings that should be widely known.
Beware of bats! The CDC reported on human rabies in the United States. Between 1960 and 2018, a total of 125 human rabies cases were reported. 36 were attributed to dog bites, all of which were bites that happened when the victims were travelling abroad. Since universal vaccination for pets was adopted decades ago, rabies in domestic pets has almost vanished. 89 cases were acquired in the U.S, and 62 (70%) of these were contracted from bats, that are by far the leading carriers of rabies in this country. Racoons were a far distant second, and foxes are also possible carriers.
Moving away from rabid bats to the much less scary but much more common problem of cardiovascular disease are findings from a number of important studies.
You don’t need to come back fasting. Traditionally, your blood lipids were always checked after an overnight fast. If you showed up having eaten breakfast, you were asked to come back to have your blood drawn. This requirement has been under question, and a recent study showed that non-fasting lipids were just as reliable a predictor of coronary disease as a fasting sample.
“White coat” hypertension needs to be taken seriously. It has long been known that some people have elevated blood pressure in the doctor’s office but normal BP when checked at home. There has been conflicting advice about whether this was a problem needing treatment. A careful analysis of many studies was published in the Annals of Internal Medicine that showed that people with so-called “white coat” hypertension ARE at increased risk if they are not on BP medication. Those on treatment for HBP who were well-controlled everywhere except in the office did not seem to be at increased risk.
Do you really need the “energy?” So-called energy drinks, which contain large amounts of caffeine among other ingredients, have been linked to increased emergency department visits, and were felt to be the cause of 34 deaths in recent years. About 30% of teenagers and 45% of deployed military personnel consume at least one of these drinks daily. Investigators had young healthy volunteers drink one of two widely sold drinks and monitored their vital signs and ECGs before and after. They reported their findings in the Journal of the American Heart Association. The energy drinks significantly raised pulse and BP in the volunteers and also prolonged the QT interval on the ECG, a change that may make the subjects more likely to have serious rhythm disturbances.
More on how diet affects health. The British Medical Journal reported on findings from the long-running Nurses Health Study. They found that increases in red meat consumption were associated with a higher risk of death, particularly so with processed meat. It is not clear that changing to “white meat” is any better. A study on healthy adults looked at cholesterol on three different diets: beef, chicken and no meat. Plant proteins had by far the most benefit, while chicken and beef were equally bad. Finally, a nutritionist from Tufts, speaking at the annual meeting of the American Society of Nutrition this month, presented evidence that inadequate intake of fruits and vegetables contributed to over 2.5 million excess deaths world-wide. Eat your fruits and veggies, folks!

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Don't be scammed by stem cells

Earlier in June, the US Food and Drug Administration (FDA) won a major legal victory by getting an injunction to prevent Florida-based US Stem Cell Clinic from offering its treatments. The company claimed to create stem cells from patients’ body fat and use these to treat a variety of serious illnesses, including Parkinson’s Disease, ALS and chronic lung disease. This company is just one of many that have sprung up like weeds offering unproven and generally ineffective treatments to desperate patients.
What are stem cells? Most of the cells in our body have only a single specific job they can do. Heart muscle cells contract and let the heart pump blood around. Bone cells provide the scaffolding that keeps us upright. Red blood cells carry oxygen around our body. None of these can do the job of the other. We do, however, have less-specialized cells that carry the potential to turn into different kinds of cells, and these act as a reserve to repair injury and replace dying cells in many tissues. True “stem cells,” derived from embryos, can become any type of cell, but there are many more partially-developed cells that can turn into some but not all kinds of cells. The best-known are so-called “mesenchymal stem cells,” more properly called mesenchymal stromal cells. These cells reside in the bone marrow, fat, liver and muscle, and can turn into bone, cartilage and fat cells. They are known to contribute to repair of damaged tissues. There is a huge amount of research looking at whether and how these cells can help alleviate human disease. As of last fall, 939 trials were registered with the NIH, the largest number (218) looking at their potential to help neurologic disease. Since mesenchymal stromal cells cannot become nerve cells, it is not certain why they have shown promise in some studies, though one guess is that they donate their mitochondria (the energy producers of the cell) to damaged nerve cells.
Mesenchymal stem cells used in trials have been obtained from bone marrow, fat and umbilical cords. Many of the trials have shown promise, but most have been done in mice, or in a very small number of people. Scientists studying this feel it is a long way before they can be considered as proven useful for humans. This, of course, never stopped a dedicated scam artist. In 2017, there were at least 700 “stem cell clinics” advertising to consumers. They were claiming to be able to cure arthritis, heart and lung disease, erectile dysfunction, Alzheimer’s disease, ALS and macular degeneration, among many other conditions. When asked, the purveyors of these treatments do not point to any trials but to “numerous success stories,” akin to a trip to Lourdes. The most common source of the “stem cells” used in these clinics is birth tissue, usually obtained by mothers who have no idea what their donation will be used for and who are not compensated for their donation. This makes it easier to convince the sufferers than if they had to have needles placed in their bodies to obtain fatty tissue samples or bone marrow cells. It must be noted that when researchers have been able to look at the products sold to the stem cell clinics, none have contained the number of live cells they claimed.
The ”practitioners” at these clinics often blur the distinction between true embryonic stem cells and the mesenchymal cells they use, claiming that their “stem cells” can turn into any tissue needed, which is clearly untrue. Up until recently, there has been little or no oversight of these “clinics” by the FDA, but hopefully that is changing. In the meantime, as your daddy used to say, “if it sounds too good to be true, it probably isn’t.” Save your money.

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B12 deficiency - the great imitator

Two recent patient experiences prompted this post. In the April 29 edition of the Wall Street Journal, Dana Hawkins-Simons described several years of being seen by specialist after specialist for her complaints of tiredness, dizziness, ringing in the ears, palpitations, shortness of breath and “brain fog.” She finally researched her symptoms and demanded that she be checked for vitamin B12 deficiency, which turned out to be the cause of her symptoms. Last month, the British Medical Journal published the case of a 69-year old woman who was diagnosed with multiple sclerosis based on her rapidly worsening symptoms of hand and leg weakness and numbness, slurred speech, poor concentration and urinary symptoms. At the center where she went for a second opinion, B12 deficiency was suspected and proved to be the cause of her symptoms rather than MS. Fortunately, she had not yet begun on the previously recommended immune-suppressive MS treatment.
Vitamin B12 is critical to many body functions. It is needed to build blood cells, and B12 deficiency was the cause of pernicious anemia, so-called because 100% of sufferers died. Dr. George Minot's discovery of the effectiveness of liver therapy in 1926 saved these people, even though no one was sure why it worked. Another pioneer working at the Boston City Hospital, Dr. Bill Castle, identified Vitamin B12 and allowed B12 injections to take the place of crude liver extracts. The neurologic system also needs B12, and deficiency can lead to many neuropsychiatric symptoms, including numbness of the extremities, an unsteady gait, forgetfulness or even dementia, irritability or depression, vision loss and a shock-like sensation down the spine with neck flexion (that is also seen in MS!). The tongue may be swollen, smooth and tender.
How does one get deficient in B12? The classic cause, commonest in elderly people, particularly those of northern European ancestry, is pernicious anemia, in which the body is unable to absorb B12 due to lack of the protein needed to allow it to pass through the intestine into the body. It was thought that dietary lack was uncommon because B12 is found in so many foods, but these are all of animal origin, and it is easy for strict vegans to become deficient if they do not take supplements. There may be decreased absorption of B12 after gastric bypass surgery or in the setting of gastrointestinal diseases such as celiac or Crohn’s diseases. Some medications, particularly the diabetes treatment metformin or long-term use of acid-suppression, may cause decreased absorption.
If you have any of the symptoms listed above, particularly if you have some the listed risk factors, you should insist on being tested. The level of B12 can be measured in the blood, but there is a wide range of “normal” and many people who are deficient may be in the low normal range. One clue may be found looking at the size of your red blood cells. If you have a patient portal or a print-out of a recent CBC (complete blood count), look for a number described as the MCV. This is short for mean corpuscular volume and describes the size of the red blood cells. Deficiency of B12 (or folic acid) typically leads to larger than normal red cells even before you become anemic. If your B12 level is below 200, you are deficient. If It is 200-300, you may be, even though the lab will list anything above 200 as normal. If your symptoms may suggest deficiency and your blood level is “low normal,” ask for further testing. This is not difficult. Another blood test, for methylmalonic acid (MMA) is almost always elevated with B12 deficiency. Be persistent. Ask to be tested – the testing is neither risky nor terribly expensive – and the consequences of missing B12 deficiency can be severe.

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The $2 million cure

You can save your baby for $2 million. Can you afford to do this? If you cannot, should we all pay?
Spinal muscular atrophy (SMA) is a rare genetic disease affecting the part of the nervous system that controls voluntary muscle movement. All types of SMA result from a single known cause, a deficiency of a protein called SMN, for "survival of motor neuron." When SMA symptoms are present at birth or by the age of 6 months, the disease is called type 1 SMA (also called Werdnig-Hoffmann disease). Babies with SMA Type 1 typically have generalized muscle weakness, a weak cry and breathing distress. They often have difficulty swallowing and sucking, and don't reach the developmental milestone of being able to sit up unassisted. These babies have two copies of the SMN2 gene, one on each chromosome 5. Over half of all new SMA cases are SMA type 1. It is a horrible disease; untreated, half of all affected infants will not live to one year of age, or if alive will require a ventilator (breathing machine). The disease affects about one in every 10,000 births, so there are about 300-400 babies born each year in the United States with this up-until-now fatal disease.
On May 24, the FDA approved a gene-based therapy for SMA-1 called Zolgensma, developed by a company that was bought by Novartis. The therapy involves injecting affected babies with an adenovirus containing a copy of the correct gene, that is taken up by the babies’ spine and theoretically cures the disease permanently. The trial which led to FDA approval was done on 22 affected babies; it showed that 21 of 22 were alive and reaching expected developmental milestones at 9.5 months of age. Untreated, 50% of these babies would not be expected to be alive at one year. For the parents of these babies, a miracle. The only fly in the ointment was that Novartis announced the treatment would be priced at $2.125 million! The only previously-approved gene therapy for an inherited disease was approved in 2017 for a rare, previously untreatable, eye disorder leading to blindness. This was priced at $425,000 for each eye. These two treatments promise (though long-term results are many years away) to cure a disease. We are now also starting to see new drugs to treat uncommon and hard-to-treat diseases that are not cures but which carry a sky-high price tag. One is Orkambi, used to treat cystic fibrosis, a hereditary disease that is treated much more easily than it used to be, though children with it are still prone to repeated lung infections. This drug clearly improves the course of patients with cystic fibrosis, but modestly, and is priced at $250,000 a year and must be taken indefinitely.
The focus of lawmakers has been, not surprisingly, on common drugs that are seeing steady price rises well above inflation, and which are taken by millions of people. Insulin is the classic example. Its price has resulted in diabetics skipping their doses and getting sicker or even dying, and this for a drug that has been in use since 1922. While pharmaceutical companies have tweaked the molecule, there have been no breakthroughs. I believe that there is enough outrage that Washington will convince or force the pharmaceutical industry to at least moderate their price increases.
What we have not yet come to grips with is how to deal with the astronomical prices of the new “breakthrough” drugs such as Zolgensma. It is hard to see a health insurer refusing to pay for a truly life saving drug. Among the many problems to be faced are how an insurance company deals with the fact that they may be paying for a drug for a patient who will not be even in their plan next year; is it fair to them? What happens if the miracle loses its luster a few years down the road. The results for Zolgensma are after less than a year of use. What happens if the effect wears off? Does Novartis have to refund some or all of the money? If we treat 350 babies a year, we are talking $700 million/year – and the U.S. already spends too much on health care. Does that money come at the price of bridges falling down? Since many of these new gene-based therapies grew out of public (NIH) funded research, it is reasonable for our elected representatives to negotiate a “fair” price that takes this into account and does not simply allow big pharma to enrich its executives and shareholders.
You remember that old Chinese curse: “may you live in interesting times.” Well, hold onto your hats. The next few years will be very interesting.

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Baby, its later than you think

A recent New York Times Op-Ed piece had the catchy title “Don’t see your doctor in the afternoon.” It was prompted by a study published in JAMA Network Open that had the much less catchy title “Association of Primary Care Clinic Appointment Time with Clinician Ordering and Patient Completion of Breast and Colorectal Cancer Screening.” The study found that the frequency of appropriate ordering of mammograms was highest (64%) for patients with 8 AM appointments and lowest (48%) for those seen at 5 PM. Similar results were seen for colorectal cancer screening, (36.5% at 8 AM and 23.4% at 5 PM). [Why so much lower for colon cancer screening is a subject for another day.] Patients did not follow through with all the recommended testing, but the trend was the same, with more patients completing the recommended tests if they had early morning appointments.
Why is this? Part of it is simple fatigue as the day goes on. Similar results were found when the National Highway Safety Administration looked at when most fatal traffic accidents occur. The evening, but not the morning, rush hour saw the greatest number of fatal accidents. Decision fatigue is used at car dealerships, where the most expensive and unnecessary options tend to be given at the end of a series of choices. Doctors, believe it or not, are human. We get tired as the day goes on, and fatigue clearly has a negative effect on decision-making. There is also the factor that primary care doctors these days have impossible workloads, with more things to be crammed into a 10-15-minute visit than can possibly be done, and the ever-lurking electronic record and its insatiable demands for data making things worse. We know that talking someone into a screening test takes time, and it is much easier to do this before we are already half an hour behind schedule.
While not recommending a screening test can be made up at a later visit, I strongly suspect that other forms of decision-making also suffer as the day goes on. It is much easier to prescribe an antibiotic that we know is not needed than to explain why the patient would be much better without it. I don’t have the data, but I would be willing to wager that more diagnostic errors are made on the last patients of the day than the first.
What can be done? Ideally, doctors would have more time for a visit and not be so rushed. In the real world, when you are scheduling your next visit, try hard to make it early in the day, before your doctor is too tired to think optimally.

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Doctor - could I have Alzheimer's disease?

As my patients aged along with me, I noticed both the expected increased numbers of people with some form of dementia and even more patients who were worried about this topic. Unless you have been away on a ten-year safari, you are very aware that dementia is a growing problem. Some 5.8 million Americans are living with Alzheimer’s Disease, and similar numbers occur in most western countries. The incidence goes up with age, and we are living longer. As I responded to a questioner recently, the only way I know of to avoid getting the disease is to die young (which I don’t recommend as a preventive strategy).
The subject gets complicated because normal aging is often accompanied by some mild memory loss. A not-unfamiliar dialog between a couple in their 70’s might be: “I was thinking we might watch a movie – the one with that actress we both like.” ”The one that starts with M?” “Yes, Meryl.” Which movie?” “Oh, the one we thought was out of her usual.” “You mean that comedy?” “Yes, about a wedding.” “OK – the Abba musical.” “That’s the one!” Mild changes in memory or less ability to quickly learn new facts are both common as we age and do not usually interfere with functioning.
There is also a condition called “mild cognitive impairment” (MCI) in which the changes in thinking and memory are more than one would expect with normal aging but not severe enough to be called dementia. The latter usually includes both memory loss and some other symptoms such as trouble with word-finding, getting lost in familiar places, inability to cope with unexpected events or handling complex tasks. Some, but by no means all, people with MCI will go on to dementia and doctors really cannot predict which will.
If a person appears to have dementia, the task of the primary care physician, often with the help of a neurologist, is to decide what is causing the dementia. While Alzheimer’s Disease is the most common, there are a variety of other brain diseases that can cause dementia. While there are some clues to be gotten from detailed brain imaging, particularly the PET scan, Alzheimer’s is in essence a clinical diagnosis, as there are no blood tests that can be used. It is important to not overlook the treatable causes of dementia. Depression can cause a “pseudo-dementia,” and a variety of medications can do this, including many that are used by the elderly. Both B12 deficiency and an underactive thyroid can cause dementia; while infrequent, testing for these is easy and reliable and should always be done once.
To complicate matters, a group of neurologists specializing in dementia have recently proposed that, particularly in the oldest group, over 80, a newly described condition they call LATE, for “limbic-predominant age-related TDP-43 encephalopathy,” may be even more common than Alzheimer’s and may co-exist with it. Their main reason for bringing this to doctors’ attention is that this condition does not respond to the medications used now to slow the progression of Alzheimer’s. The main reason in general to try to make a specific diagnosis is to guide treatment. There are no cures for Alzheimer’s or most of the other dementing illnesses. The medications we have are modestly useful in slowing the inevitable progression of the disease, but that is all they do.
Can you ward off Alzheimer’s without dying young? About all we know is that regular exercise does lower the incidence of dementia, and that a healthy plant-based diet also has modest protective effect. Keeping the brain busy by learning new things is also probably helpful.
So, if your only problem is occasionally forgetting where you left the keys but do find them, you can relax. You probably do not have Alzheimer’s. Get out there and exercise, eat healthy and learn a new language.

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