Monday, January 20, 2020

Age-related low testosterone has limited treatment indications

Is age-related low testosterone normal or a disease? If it is a disease, what are the benefits and harms of testosterone therapy? A previous AFP Community Blog post reviewed the controversy surrounding screening for low testosterone in older men and the U.S. Food and Drug Administration's requirement that prescription testosterone product labeling include warnings about a possible increased risk of heart attacks and strokes. A recent analysis of Medicare data found that testosterone prescribing peaked in 2013 and has since declined, but that prescribing rates were actually higher for men with coronary artery disease (CAD) than men without CAD. Meanwhile, another study suggested that men prescribed testosterone therapy have an increased risk of developing venous thromboembolism (blood clots in the legs or arms that can migrate to the lungs) in the first 6 months of use.

Earlier this month, the American College of Physicians (ACP) published a clinical practice guideline, endorsed by the American Academy of Family Physicians (AAFP), to provide evidence-based recommendations for primary care and subspecialist clinicians on treatment of men with age-related low testosterone. Based on an independent systematic review of the efficacy and safety of testosterone treatment, the ACP and AAFP suggested that clinicians discuss potential benefits, harms and costs of therapy with patients with age-related low testosterone and sexual dysfunction. The guideline recommended against initiating testosterone treatment for the purpose of improving energy, vitality, physical function, or cognition, due to the lack of benefits in randomized trials. Since some men will not respond to treatment, the guideline suggested re-evaluating symptoms within 12 months of initiating testosterone therapy, and discontinuing treatment if sexual function does not improve.

Studies assessing patient preferences reviewed by the ACP showed mixed preferences for injectable versus topical testosterone; the most bothersome symptoms were erectile dysfunction, decreased sex drive, and loss of energy; and high therapy discontinuation rates in two studies (30 and 62 percent). Since transdermal testosterone costs an average of 14 times as much as intramuscular ($2135 vs. $156 for a year's supply in 2016, respectively) and has similar clinical effects and harms, the ACP and AAFP suggested considering intramuscular rather than transdermal formulations.

Testosterone therapy has a vocal online constituency that holds strong beliefs in its effectiveness despite contradictory evidence, as I learned when I advised against its widespread prescribing in a Medscape commentary a few years ago. Although the ACP guideline did not directly address the relatively common phenomenon of testosterone treatment in men without low testosterone levels, the American Society of Clinical Pathology, the American Urological Association, and the Endocrine Society have all advised against this type of prescribing to improve erectile dysfunction or any other symptom.


This post first appeared on the AFP Community Blog.

Wednesday, January 15, 2020

When a cancer diagnosis predicts future good health

The American Cancer Society recently reported the largest recorded one-year decline in the U.S. cancer death rate (2.2 percent) from 2016 to 2017, driven by lower lung cancer and melanoma mortality. Although the relative contributions of screening / early detection, changes in risk factors (e.g., smoking, sunscreen use), and new cancer therapies can be debated, the continuing decline is positive for these patients, even in the context of troubling increases in overall death rates.

Despite this apparent progress, hardly anyone would call a cancer diagnosis "good news." But as my longtime readers know, all cancers are hardly created equal. Some are almost invariably lethal, some are "cancer" in name only, and most reside somewhere in between. A less heralded research letter in JAMA Internal Medicine in December presented relative and disease-specific survival statistics of 10 early-stage cancers in three illustrative graphs. (I wish that I could reproduce the figures here, but the American Medical Association takes copyright infringement quite seriously and requests prohibitive fees for reprinting its content, even if the data are derived from a public source such as the National Cancer Institute's Surveillance Epidemiology End Results (SEER) registry - which these are.)

Dr. Andrea Marcadis and colleagues found three patterns in the SEER data from 2004 to 2015. The first one you might expect: for early oral cavity/pharyngeal, bladder, and lung/bronchus cancers, relative survival (comparing survival of a cancer population to that of a matched population without cancer) was worse than disease-specific survival (the proportion of patients not dying of their cancer), likely related to a higher smoking prevalence in these patients. The second pattern, which held true for testicular and pancreatic cancer, showed relative survival that was similar to disease-specific survival, even though the prognosis of testicular cancer is generally excellent, while the prognosis of pancreatic cancer is usually terrible.

The third pattern was the most interesting: for early prostate, breast (including ductal carcinoma in situ, which was considered separately), thyroid cancer, and melanoma, relative survival was not only better than disease-specific survival, but greater than 100%. In other words, patients with these particular early cancer types were more likely to survive than similar individuals without cancer.

How can a cancer diagnosis possibly predict future good health? The answer emerges from what these cancers have in common that the others don't: we screen patients for them, even though the evidence of net screening benefit varies quite markedly. Patients who undergo regular screening are also more likely to follow their doctors' advice and practice other health-enhancing behaviors. The researchers noted:

These statistics can help physicians explain to certain patients that their actions prior to diagnosis may mean more for their survival than the diagnosis itself. This may be reassuring and mitigate the risk of depression and anxiety associated with cancer diagnosis. ... Relative survival may help patients reorient their expectations by providing a comparison to a similar person without cancer, revealing that not every cancer diagnosis necessarily portends an earlier death.

I don't mean to suggest that anyone welcome a cancer diagnosis. Even cancers with a great relative prognosis cause emotional stress, more medical visits and expenses, potentially uncomfortable or risk-associated diagnostic procedures, and possibly chemotherapy, radiation therapy, or surgery. But it's critical for patients and clinicians to understand that some cancer (over)diagnoses are more the result of doctors looking too hard for them (see South Korea's "thyroid cancer epidemic" caused by an ill-advised national screening program) than one's genetics or behavior.

Wednesday, January 8, 2020

Becoming a better doctor

For the most part, I don't make New Year's resolutions. I've always thought that the beginning of a calendar year was an arbitrary time to decide to start or stop doing something, and despite being the start of a new decade, 2020 feels no different. However, for the past several months, I have been working on a few professional self-improvement projects that I hope will make me a better doctor in the long term.

Last fall, I completed a training course through the Providers Clinical Support System and obtained my DATA waiver in order to provide medication-assisted treatment with buprenorphine to patients with opioid use disorder (OUD). As I observed in a Medscape commentary last year, some patients with chronic pain will continue to need long-term opioid therapy, and a certain percentage of them will eventually progress to misuse and OUD. And that doesn't include many others who become dependent on illicit opioids. Buprenorphine is an effective and evidence-based treatment that allows many patients to attain remission of their disease and put their lives back together, and as illustrated in a recent issue of the Journal of the American Board of Family Medicine, family physicians are increasingly equipping themselves to provide it, much as primary care took on the responsibility of caring for victims of the AIDS epidemic in the 1980s.

As intravenous drug use has fueled the opioid overdose epidemic, it has also been driving up rates of chronic hepatitis C virus (HCV) infections in young adults. Since September, I have been participating in a Project ECHO program through Medstar Health that is training primary care clinicians to manage or co-manage adults with HCV in Washington, DC and Maryland. Although I have expressed skepticism in the past about widespread one-time screening for HCV (and remain uncertain that the evidence supports the U.S. Preventive Services Task Force's proposed expansion of screening to all persons age 18 to 79 years), I'm also very much aware that this disease isn't going away without treatment. As the prices of antiviral drugs come down and states come up with creative ways to finance bulk purchasing for Medicaid recipients, more family physicians should acquire the skills to treat these patients.

Finally, while serving on my medical school's Subcommittee on Faculty Diversity & Inclusion, I became interested in how implicit (unconscious) bias affects not only faculty recruitment, but student and employee recruitment, mentoring, and promotion; workplace culture; and contributes to health disparities through effects on patient care. I joined our inaugural Bias Reduction and Improvement Coaching (BRIC) train-the-trainer program in part to better understand how to mitigate negative consequences of unconscious biases on my own students and patients.

Thursday, December 26, 2019

My favorite health and health care books of 2019

Looking for some good reads for this holiday season and the coming year? Here is my annual top ten list of health and medicine-related books (read, not necessarily published, in 2019), in alphabetical order. I've provided links to the publishers' websites for your convenience, but I don't receive any financial incentives or extra web traffic if you buy these books from them. So if one or more catch your fancy, feel free to pick up a used copy on Amazon or a free one at PaperBackSwap or your local library.


1. The Addict: One Patient, One Doctor, One Year, by Michael Stein

2. Bellevue: Three Centuries of Medicine and Mayhem at America's Most Storied Hospital, by David Oshinsky

3. Crisis in the Red Zone: The Story of the Deadliest Ebola Outbreak in History, and of the Outbreaks to Come, by Richard Preston

4. Deep Medicine: How Artificial Intelligence Can Make Healthcare Human Again, by Eric Topol

5. Patient H.M.: A Story of Memory, Madness, and Family Secrets, by Luke Dittrich

6. Priced Out: The Economic and Ethical Costs of American Health Care, by Uwe Reinhardt

7. Radical: The Science, Culture, and History of Breast Cancer in America, by Kate Pickert

8. Recapturing Joy in Medicine, by Amaryllis Sanchez Wohlever

9. Vaccines Did Not Cause Rachel's Autism: My Journey As a Vaccine Scientist, Pediatrician, and Autism Dad - Peter Hotez

10. Well: What We Need to Talk About When We Talk About Health, by Sandro Galea

Saturday, December 14, 2019

Proposals to lower prescription drug prices: too little, too late?

A bright spot in the annual U.S. health spending report published last week by the Centers for Medicare and Medicaid Services (CMS) was a 1% decrease in retail prescription drug costs from 2017 to 2018, due to greater use of generics and a slower rise in brand-name prices. According to CMS, this was the first time that these costs have declined since 1973. A previous American Family Physician Community Blog post described ongoing efforts by physician groups, payers, and government to restrain rising drug prices; a 2017 editorial reviewed actions that individual health professionals could take to help patients; and a 2019 editorial discussed the high costs of insulin and what family physicians can do. It's possible that some of these efforts are beginning to bear fruit.

Prescription drug prices vary considerably across pharmacies, geographic regions, and even within the same town or metropolitan area. A cross-sectional study of cash prices for 10 common generic and 6 brand-name drugs in the fall of 2015 obtained using the online comparison tool GoodRx (which AFP uses to estimate drug prices) found that generic drugs were least expensive in big box pharmacies, followed by large chain (more than 100 retail locations) and grocery pharmacies, while small chains (4 to 100 stores) and independent pharmacies had the highest prices. For example, the mean price of one month of generic simvastatin 20 mg was $35 at big box pharmacies, $42 at large chains, $50 at groceries, $112 at small chains, and $138 at independent pharmacies. Cash prices for brand-name drugs varied less; one month of esomeprazole (Nexium) 40 mg, for example, cost between $302 and $345 across pharmacy types.

The American College of Physicians recently joined a growing number of groups advocating that CMS be given the authority to directly negotiate drug prices in Medicare Part D, which is currently forbidden by law. In contrast, the Department of Veterans Affairs (VA) Health System already controls prescription costs through direct negotiation and a closed formulary. A study in JAMA Internal Medicine calculated that in 2017, Medicare could have saved $1.4 billion on inhalers for asthma and chronic obstructive pulmonary disease by paying lower VA-negotiated prices, and $4.2 billion if it had paid VA prices and instituted the VA formulary.

But what about the pharmaceutical industry's assertion that lower negotiated prices would stifle innovation and reduce incentives for drug development? In a recent commentary, Dr. Peter Bach proposed that CMS adopt a "too little" or "too late" strategy, selectively negotiating prices of drugs that have either received conditional FDA approval based on a surrogate rather than a patient-centered outcome ("too little") or have passed their guaranteed 5-year period of FDA monopoly protection ("too late"). In 2019, if CMS had negotiated the prices of the top 10 most costly drugs in each category down to those in the United Kingdom (an average savings of 57%), Dr. Bach estimated that it could have saved $1 billion on the 10 "too little" drugs and $26 billion on the 10 "too late."

The potential savings are substantial. But compared to the staggering $336 billion the U.S. collectively spent on prescription drugs in 2018, are these proposed pricing reforms too little, too late?


This post first appeared on the AFP Community Blog.

Wednesday, December 4, 2019

The health dividend: reducing medical waste to improve population health

For  most people, the term "medical waste" probably brings to mind images of discarded syringes, soiled gauze and bandages, and garbage containers filled with the ubiquitous plastic packing for sterilized instruments. They probably don't think about inconceivably large piles of money evaporating into thin air. But in addition to having the most expensive health care system in the world, the U.S. also leads the world in wasted health care spending. In a recent analysis in JAMA, Dr. William Shrank and colleagues updated prior estimates based on published literature from 2012 to 2019 and concluded that approximately 25% of national health care spending, or about $800 billion each year, is wasted. The main culprits are administrative complexity ($266 billion); excessively high prices ($231-$241 billion); failure of care delivery ($102-$166 billion); overtreatment or low-value care ($76-$101 billion); fraud and abuse ($59-$84 billion); and poor care coordination ($27-$78 billion).

These are huge amounts of money. When American life expectancy has been falling for three consecutive years after more than half a century of steady increases, it would seem that reallocation to population health initiatives of the portion of health care waste that is potentially recoverable with existing interventions, $191 to $282 billion according to the JAMA study (by comparison, annual funding for the Affordable Care Act's Prevention and Public Health Fund has yet to exceed $1 billion), would go a long way toward addressing the root causes of increasing premature deaths - problems such as poverty, segregation, and low social support which comprise the actual causes of death in the U.S.

So why don't we? In an accompanying editorial, former CMS administrator Dr. Don Berwick hit the nail on the head:

What Shrank and colleagues and their predecessors call “waste,” others call “income.” ... When big money in the status quo makes the rules, removing waste translates into losing elections. ... For officeholders and office seekers in any party, it is simply not worth the political risk to try to dislodge even a substantial percentage of the $1 trillion of opportunity for reinvestment that lies captive in the health care of today, even though the nation’s schools, small businesses, road builders, bridge builders, scientists, individuals with low income, middle-class people, would-be entrepreneurs, and communities as a whole could make much, much better use of that money.

Living in Washington, DC during the Great Recession of 2007-2009, I observed that the only two industries that managed to thrive and expand during those otherwise dismal years were the federal government and health care. While that was good for me personally, as a health care professional then employed by the federal government, it also meant that billions of dollars that otherwise could have contributed to the economy and individual incomes were, as Dr. Berwick noted, "captured" by the health care industry, most clearly in the form of rising costs of health insurance.

After the collapse of the Soviet Union and the end of the Cold War, Presidents George H. W. Bush and Bill Clinton both talked about a "peace dividend" consisting of lower military spending that could be diverted into other government programs, used to pay down budget deficits, or returned to the people in the form of lower taxes. Although it is debatable how much the military-industrial complex really shrunk in the 1990s, the gargantuan health care-industrial complex is likely to be at least as tenacious, if not more, in resisting efforts to reduce wasteful spending in order to generate a "health dividend" for all Americans.