Friday, September 13, 2019

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.

Prescription for Bankruptcy. Buy the book on Amazon

Saturday, August 31, 2019

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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Tuesday, August 20, 2019

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.

Prescription for Bankruptcy. Buy the book on Amazon

Monday, August 12, 2019

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.”

Prescription for Bankruptcy. Buy the book on Amazon

Sunday, August 4, 2019

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.

Prescription for Bankruptcy. Buy the book on Amazon

Saturday, August 3, 2019

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.”

Prescription for Bankruptcy. Buy the book on Amazon

Tuesday, July 23, 2019

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.

Prescription for Bankruptcy. Buy the book on Amazon