Link to your favorite references from the AFP home page!

- Jennifer Middleton, MD, MPH

When I was a resident 10 years ago, I carried several references in the pockets of my white coat. My Palm pilot was useful for referencing medical equations but little else, so I carried everything else in paperback: a drug reference guide, an antibiotic guide, a book on common on-call patient situations. Online reference tools were in their infancy, and by the end of my intern year several pages in those books were dog-eared and memorized.

Fast forward to 2015: my smartphone contains all of those resources and more - I don't even have to carry a printed patient census in my pocket anymore when I round in the hospital. But as nice as smartphones are, nothing beats the full view of a webpage on a computer screen, and we have endless options of medical reference websites at our fingers. Answering clinical questions at the point-of-care is easier than it's ever been, but keeping track of those websites can be difficult. Sure, you can add bookmarks to your web browser, but some health systems limit the ability to access those behind their firewalls. Plus, it takes time to bring those up and log in.

What if you could pull up a trusted website and access all of your favorite references right there? AFP recently added the ability to do precisely that - on the right side of the top banner with a gold star is the new "Favorites" section. If you're logged in to the AFP website (which you can do once and leave it if you're working on a trusted computer), clicking on "Favorites" will bring you to a page where you can quickly paste in the hyperlinks of whatever references you'd like to include - be they AFP sites or others.

AFP By Topic and the Choosing Wisely tool are available from the AFP homepage, so I decided not to add those to my Favorites list. I did add AFP's Medicine by the Numbers webpage, along with our new Podcasts. I suspect that the CME Quiz and Photo Quiz department pages will be popular on many AFP subscribers' Favorites. I've also added my prescription drug database of choice and a couple of subscription online clinical information resources to round out my list.

Answering questions quickly at the point-of-care is easier than ever with the AFP Favorites feature, as is accessing your favorite medical content when you have a little more time to peruse it. If you'd like a full tour of all of the updates to the AFP website, including the Favorites feature, you can find it here.

Pharma industry free speech is anything but free

- Kenny Lin, MD, MPH

Last month, the American Medical Association (AMA) called for a ban on direct-to-consumer (DTC) advertising of prescription drugs and medical devices, arguing that this type of advertising drives the nation's escalating drug bill by creating demand for new, expensive medications that are often no more effective than older ones. Since the first televised prescription drug ad aired in the U.S. in 1983, pharmaceutical companies have spent billions of dollars on DTC advertising, including $4.8 billion in 2014. The ads are worth every penny. According to Kantar Media, 76% of Americans have seen at least one DTC ad on television in the past 12 months, and 1 of 3 who viewed these ads took some action as a result.

The AMA's call comes at a time of increasing public concern about the potentially harmful impact of loosening restrictions on marketing and promotion of off-label use of drugs. Although the U.S. Food and Drug Administration (FDA) has historically prohibited this practice, earlier this year a federal District Court judge blocked the FDA from enforcing restrictions on promoting a prescription fish oil product for an unapproved indication. The judge determined that if the FDA refused permission to distribute the promotional materials, it would violate the company's First Amendment right to freedom of speech.

Although recent Supreme Court decisions have established that for some purposes, corporations have the same rights as people, there are real dangers to allowing the pharmaceutical industry to claim anything they want about their products to physicians or consumers under the guise of free speech. A Canadian cohort study published in JAMA Internal Medicine found that off-label drug use was 44 percent more likely to be associated with adverse drug events than on-label use, a difference driven almost entirely by the prescription of drugs without strong supporting scientific evidence (about 80 percent of all off-label prescriptions). The top five drugs used off-label were quinine, gabapentin, quetipine, amitriptyline, and risperidone.

A 2014 American Family Physician editorial by Drs. April Fitzgerald and Patrick O'Malley discussed how family physicians can "stay on track when prescribing off-label." The authors noted that the toughest calls occur when evidence suggests potential benefits but the harms are not well described:

The ethics surrounding off-label use become more complicated when considering medications with less clear-cut positive or negative risk-benefit ratios. This is the gray area where physicians individually weigh the translational gaps in evidence between effectiveness, available research, and the complexities of real-world clinical practice. Particular scrutiny is suggested when using off-label medications with red flags, such as new medications, medications with known serious adverse effects, or high-cost medications, or when considering novel off-label use.

Pharmaceutical free speech is actually anything but free. By directly encouraging patients to request new medications from physicians, and by promoting drugs for unapproved uses, the industry will not only continue to increase national spending on prescription drugs, but expose even more patients to an unacceptable risk of iatrogenic harm.

What is the best diuretic for treating hypertension?

- Jennifer Middleton, MD, MPH

Even though hydrochlorothiazide (HCTZ) was the 10^th most commonly prescribed drug in the US in 2010, an FPIN Help Desk Answers article in the current issue of AFP argues in favor of chlorthalidone over HCTZ, as does a 2008 AFP editorial. Although some studies have found HCTZ and chlorthalidone's effects on cardiovascular mortality to be equivalent, some studies have found chlorthalidone to be more effective. 

The AFP FPIN Help Desk article reviews two systematic reviews and one randomized controlled trial (RCT) comparing HCTZ and chlorthalidone for reduction of coronary heart disease (CHD) events. The first systematic review and the RCT both showed greater blood pressure lowering with chlorthalidone compared with HCTZ, but neither measured cardiovascular outcomes. The second systematic review included a network analysis comparing outcomes from studies that used chlorthalidone to studies that used HCTZ. Those researchers found that the number needed to treat (NNT) with chlorthalidone instead of HCTZ to prevent 1 additional cardiovascular death over 5 years was 27.

Some cohort studies have found chlorthalidone non-inferior to – and potentially more hazardous than – HCTZ. A 2013 prospective cohort study conducted in Canada found no difference in cardiovascular outcomes but a higher risk of hospitalization for hypokalemia; interestingly, patients on chlorthalidone were more likely to be on a beta-blocker than those on HCTZ because of a combination pill on the Canadian formulary. A retrospective cohort study reviewed by AFP in 2013 found equivalent outcomes between patients treated with chlorthalidone versus those treated with HCTZ.

These cohort studies showing equivalence between chlorthalidone and HCTZ, along with concern for more hypokalemia with chlorthalidone, may explain why HCTZ is the diuretic of choice in treating hypertension in the US.  In the level of evidence hierarchy, cohort studies sit below randomized controlled trials (RCTs) and systematic reviews because they are more prone to bias. On the flip side, however, cohort studies can sometimes provide better information about "real life" conditions; in an RCT, participants follow strict protocols, but in cohort studies, we can measure the effect of interventions as they play out in practice.  

So, overall, some cohort studies have found HCTZ and chlorthalidone to be equivalent, but some RCTs and systematic reviews have found differently. Some studies have shown increased hypokalemia with chlorthalidone use, but several large hypertension treatment trials, including the 2015 SPRINT, preferentially used chlorthalidone in their treatment protocols.  If you’d like to read more, there’s an AFP By Topic on Hypertension.

When the evidence base is conflicting, it can be challenging to decide what to do in practice. How do you decide which diuretic to prescribe for patients with hypertension?

Guest Post: Primary care lifeline

- Sarah E. Stumbar, MD, MPH

In March, the Association of American Medical Colleges (AAMC) released a report estimating that there would be a shortage of between 12,500 and 31,100 primary care physicians by 2025. These projections are not news to anyone in medicine, but in the uproar following Columbia University/New York-Presbyterian’s unilateral decision to close its family medicine residency program (and the subsequent quick reversal of that decision), it became obvious that most people still do not understand the complex and integral roles that primary care physicians play in their patients’ lives.

During my Family Medicine residency, I provided prenatal care, delivered babies, provided postpartum contraception, performed options counseling and abortions, and saw the infants I delivered grow into toddlers. I went on home visits to provide emotional support and end-of-life care to a magnificent woman dying of esophageal cancer. I followed my patients from the clinic to the inpatient setting and back to the clinic again. I worked to forge relationships that would hopefully keep my patients out of the hospital. I gave out my cell phone number and my e-mail address, and I welcomed phone calls and clinic walk-ins whenever there was a question or concern. I made countless calls to specialists, begging them to see my patients sooner than the next available appointment in six months. Once, for a patient with possible lung cancer on a CT scan, I made twelve phone calls to a pulmonologist before I was able to get her an appointment within an acceptable amount of time. In the Bronx community where I trained, I made certain that I was the strongest advocate for my patients, many of whom had never had anyone advocate for them before.

Now seeing uninsured patients in a mobile health clinic in Miami-Dade County, I am the safety net that wouldn’t otherwise exist. My new patients are quickly learning that I believe in their right to health care, and I will do anything to help them navigate our struggling medical system. The Washington Heights Community served by Columbia’s deeply invested residents—and this nation as a whole—needs more family physicians, not more medical administrators who have forgotten the daily realities of our patients.

**

Dr. Stumbar is a 2015 graduate of Montefiore Medical Center’s Residency Program in Social and Family Medicine. She is now an Assistant Professor of Family Medicine at Florida International University in Miami.

Which patients should SPRINT to a systolic goal of 120?

- Jennifer Middleton, MD, MPH

Two weeks ago, I wrote about the controversy surrounding the early closure of SPRINT. That same day, the SPRINT research group published the results of their study; for SPRINT participants, a systolic blood pressure (SBP) goal of 120, compared to 140, resulted in lower risk of several cardiovascular events including mortality, but we should proceed with caution before applying these findings to our patients.

SPRINT was a randomized controlled trial that enrolled over 9000 community-dwelling participants across 102 clinical sites in the United States. Participants had to be at least 50 years old, have a SBP between 130 and 180, and had to have "an increased risk of cardiovascular events," which the research group defined as prior cardiovascular disease (CVD) excluding stroke, chronic kidney disease (CKD), a 10-year Framingham risk score of at least 15%, or age of at least 75 years. Participants were excluded if they had diabetes or a history of a stroke. The research group provided a suggested protocol for antihypertensive medications. Participants in the intensive group had a mean SBP of 121.4 mmHg, and participants in the control group had a mean SBP of 136.2 mmHg.

The researchers' primary outcome was a composite of myocardial infarction, acute coronary syndrome, stroke, heart failure, or death from CVD, and the rate of the composite outcome was lower in the intensive group (hazard ratio 0.75 [0.64-0.89]). The number needed to treat to prevent a primary outcome event was 61. The intensive treatment group also had a higher likelihood of worsening renal function, and since the study was stopped early, it's impossible to know how likely it is that those renal effects would be irreversible. Other adverse events more common in the intensive treatment group: hypotension, syncope, and electrolyte abnormalities.

The study population may not be generalizable to your practice; it's important to note that these findings should not be extrapolated to suggest that all of our adult patients should aim for SBPs below 120. Certainly, that may be a reasonable goal for patients over the age of 50 with "an increased risk of cardiovascular events," but I suspect that many of our patients over the age of fifty with hypertension (and without diabetes) do not have those risk factors. Those patients who do meet the study parameters should still engage in patient-centered decision making regarding the risks of intensive treatment.

Dr. Lin commented on other challenges of applying this study to our patients; office blood pressure measurements, for example, are rarely done with the level of precision they were measured with in SPRINT. Aggressively adjusting medication doses based on what may be inaccurate office BP readings could potentially cause patients significant harm. Most of the time, the JNC 8 guidelines are likely to be more applicable to the patients in our offices than SPRINT's narrowly defined parameters.

Has SPRINT changed how you treat hypertension?

Two perspectives on the PSA screening pendulum

- Kenny Lin, MD, MPH

Two research studies published today in JAMA presented compelling evidence that the 2012 U.S. Preventive Services Task Force recommendation statement that discouraged prostate specific antigen (PSA)-based screening for prostate cancer has had a significant impact on clinical practice. In one study, researchers from the American Cancer Society used data from the Surveillance, Epidemiology, and End Results registries to document an 18% relative decrease (from 37.8% to 30.8%) from 2010 to 2013 in the percentage of men age 50 years and older who reported PSA screening in the previous 12 months. In another study, a separate team of investigators found a similar decline in the prevalence of PSA screening reported in the National Health Interview Survey in men age 50 to 74 years.

For me, and for other proponents of the view that PSA screening is not effective in reducing mortality from prostate cancer and instead leads to substantial psychological and physical harms, this reversal in practice is good news. In an editorial published in the October 15th issue of American Family Physician, Dr. Vinay Prasad argued that family physicians who reduce or discontinue their use of the PSA test for screening are on solid ground:

When it comes to PSA screening, the pendulum has swung. Not only has our understanding of the benefits and harms shifted, as reflected by a continual change in guidelines away from testing, but the burden to justify screening has also swung. For decades, critics of PSA testing have shown the many unintended repercussions of the test, cautioning that our initial widespread adoption was not justified. Moving forward, it must be the proponents of screening who shoulder the burden of proof. Their task will be to show in a future randomized study whether any PSA screening algorithm can improve survival or quality of life compared with what is now the standard of care—no routine screening. Before primary care physicians consider reintroducing the PSA test, they must have proof that it improves outcomes.

In another editorial that accompanied the JAMA studies, Dr. David Penson also described the shift in practice as a "pendulum," but took the position that until a better screening test is developed, "the PSA test can be deployed more effectively (or strategically), maximizing benefit while minimizing harm." If PSA screening does in fact save some lives, Dr. Penson argued, then extending screening intervals and focusing on men who are more likely to develop "high-risk" prostate cancer could be a better approach than not screening at all:

Certainly, physicians have been overly aggressive in their approach to prostate cancer screening and treatment during the past 2 decades, but the pendulum may be swinging back the other way. It is time to accept that prostate cancer screening is not an “all-or-none” proposition and to accelerate development of personalized screening strategies that are tailored to a man’s individual risk and preferences. By doing this, it should be possible to reach some consensus around this vexing problem and ultimately help men by stopping the swinging pendulum somewhere in the middle.

Where is your practice on the pendulum of PSA screening?