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January 21st, 2012

More Medical Testing! No, Less! You Decide

Fascinating Yin-Yang this week on the issue of medical testing. Want more? Want less?

First, this remarkable piece on retail medical labs, including a description of a company called ANY LAB TEST NOW:

Labs where folks can just walk in and order tests on themselves are popping up in retail centers across the country… At Any Lab Test Now, co-owner Anthony Richey pulls out a long sheet of paper with all the different tests his lab offers. There’s everything from an HIV screening to a “fatigue” panel. It looks like a sushi menu. “You say, ‘Well I want to check my diabetes, I want to get a hemoglobin A1C, and maybe I’ll check my lipid panel. And I’m a male over 40 so I’ll get my PSA checked,’ ” Richey says.

On the company’s web site, there are plenty of smiling, healthy people, plus these appealing claims:  “No Doctor’s order needed … No appointment necessary … No insurance needed …  Most results available in 24-48 hours.”

No doubt this is excellent customer service. But care to guess what that “Fatigue Panel” will set you back? That will be $499, thank you very much. But maybe they offer Gift Cards, that should help.

And if anything comes back abnormal?

If your results are ‘abnormal’ or ‘out-of-range’ from the normal, please contact your physician.

Joy.

It’s a poorly appreciated fact that the lower the likelihood of a disease being present, the greater the chance of a false-positive result.

Which is why no sensible physician would order all the components in the “Fatigue Panel” — which of course includes Lyme and EBV testing — without first taking a thorough history to determine if these diseases are even worth considering.

Meanwhile, over in the Annals of Internal Medicine, a group from the American College of Physicians this week argues for less testing:

The overuse of some screening and diagnostic tests is an important component of unnecessary health care costs… Efforts to control expenditures should focus not only on benefits, harms, and costs but on the value of diagnostic tests—meaning an assessment of whether a test provides health benefits that are worth its costs or harms.

What follows is an entirely sensible view of medical testing, with certain problematic, “low-value” tests called out for being wasteful — including the Lyme test mentioned in that “Fatigue Panel.”

And those false-positive tests, which retail labs must be generating by the crateload every day?

False-positive results are of concern because they often lead to further testing, which may be expensive and potentially harmful. They may also create anxiety for the patient and may lead to inappropriate treatment.

Which brings us back to the primary motivation of ANY LAB TEST NOW, which must be obvious by now:

“From a marketing standpoint it’s a good position to be in where you create a service, create a demand,” says Rodney Forsman, president of the Clinical Laboratory Management Association. “It becomes a consumable like Starbucks or bottled water.”

My advice? I strongly recommend that someone from ANY LAB TEST NOW contact the guys running GNC and explore co-franchising options.

They completely deserve each other.

January 18th, 2012

ID Case Conference Discussant Types

We specialists in Infectious Diseases love case conferences — especially those where the case is presented as an “unknown”, and we try to figure out the diagnosis from the history.

I suppose this isn’t very surprising, since ID cases in general are already among the most interesting in all of medicine. Those that are case-conference-worthy are particularly prime.

“Funny bug in a funny place,” was how one of my colleagues characterized these cases.

After the case is presented, the discussion by the participants takes various forms. I’ve been to hundreds of these conferences over the years, and have noted that the path taken by the discussants to arrive at the diagnosis (or not) varies quite a bit. There are certain styles, certain patterns of medical thinking in the conference room (rather than in the exam room or at the bedside) that show up again and again:

  • The instinctual, “Here’s the diagnosis” approach. Very valuable when spoken by the Giants in the Field, who usually have several decades of clinical experience. These are short, targeted discussions that impressively even list the possible diagnoses in order of likelihood. Lou Weinstein was the quintessential “here’s the diagnosis” guy; sadly I only got to hear him discuss cases in the last few years of his distinguished career. Not surprisingly, this kind of medical reasoning doesn’t work nearly as well when attempted by relative beginners, e.g., a medical student, or even a second-year ID fellow. Bottom line: Beware the clinician in his/her 20s who begins a case discussion with the phrase, “In my clinical experience …”
  • The comprehensive, “I’ve considered the entire universe of living organisms” approach. Can be both spectacularly interesting and educational or, conversely, crushingly, mind-numbingly boring. Mort Swartz (another Giant in the Field) discusses cases in this style, and I learn something from Mort every time — his knowledge not only of ID but all of Internal Medicine is awe-inspiring. However, my heart always sinks when a mere non-Mort mortal (couldn’t resist) starts a discussion by listing all the main categories of microorganisms as a prelude:  “Let’s see, as potential causes for this person’s infected hip, there are prions, viruses, aerobic and anaerobic bacteria, higher bacteria, mycobacteria, fungi, algae, protozoa, helminths, ectoparasites …” Time to get some more coffee.
  • The prodding, “Let’s stop this game and tell me the diagnosis” approach. Usually goes something like this: A generic case is presented with minimal information — let’s say a man with a skin infection. No further history is given. And the discussant, not surprisingly, prods the presenter to give more information. “Any cats?” he/she asks, thinking Pasturella multocida or bartonella. “Any water exposure?” thinking Aeromonas hydrophila or Vibrio vulnificus. Because the discussant knows a simple skin infection is never going to make it to case conference, he/she keeps searching — there MUST be something interesting about the epidemiology. The presenter relents: “Well, as it turns out, the patient works as a clam shucker.” Bingo, Mycobacterium marinum or Erysipelothrix rhusiopathiae.
  • The diverting “I don’t know what this diagnosis is, but I certainly know a lot about other stuff, so let’s talk about that” approach. This clever strategy usually involves a true expert in a field forced out of his or her comfort zone. The world expert on salmonella, for example, suddenly finds him/herself discussing a hospital-acquired pneumonia in a patient who’s just had cardiac surgery. You can be sure that eventually the subject of intracellular pathogens (of which salmonella is an excellent example) will come up — somehow.
  • The deer in a headlights, “You talking to me?” approach. Happens frequently when someone gets called on to discuss a case who’s not expecting it. Perhaps they’re junior faculty. Or just shy. Or maybe their mind has wandered, and they’re thinking about the Patriots’ playoff game, or whether to have another muffin, or the Krebs cycle. (I have never spontaneously thought about the Krebs cycle — see Figure above for a refresher.) And I’ve been informed by one of my most esteemed colleagues that some people just hate being called on, which I totally respect. (But others love yacking away during conference — they get offended if they’re not asked to opine — so it would be helpful to know how people feel about this. A green sticker on your white coat, perhaps, one that reads, “CALL ON ME!”) Suffice to say the startled discussant rarely gets the diagnosis correct, but they are often inadvertently funny.

Here’s a tip — if you’re ever asked about a case during conference, and you haven’t been listening, and the person being discussed is acutely ill, just say, “It could be staph.” If chronically ill, “It could be TB.” You will never be wrong.

What kind of discussant are you?

January 10th, 2012

First Rabies Case in State in Over 75 Years Raises Questions (Again) About Preventive Strategies

The recent case of bat-related rabies in a Barnstable man has prompted my colleague Larry Madoff, director of the Division of Epidemiology and Immunization at the Mass Department of Public Health, to write this fine commentary in the Atlantic.

I particularly like these passages:

Rabies is perhaps the archetypal zoonotic disease, one spread between animals and humans. It has an extremely broad host range, with the ability to infect all mammals. The ancients understood that when a mad dog bit another dog, it too became mad … While rabies is transmissible between any species, most transmission occurs within the species — bat to bat, raccoon to raccoon — and the virus adapts slightly to its host. That means each virus carries a signature in its genetic sequence indicating the species and geographic location of the “donor.”

He also states, “Keeping bats out of our homes, particularly our sleeping quarters, is a key public health measure in reducing human rabies.”

But as I’ve written before, I’m not so sure the numbers back this up as an effective preventive measure — or at least one we can quantify. Sure, we should try to keep bats out of our bedrooms, and I’d be quick to get immunized if one bit me.

But will these individual efforts — or the recommended practice of giving rabies immune globulin plus the vaccine series for “bats in the bedroom” exposures — actually reduce the number of rabies cases? Maybe not.

To recap the logic in this Canadian study:

  • Bats in houses — incredibly common.
  • People seeking preventive immunization with bats in the house — very rare (though some summer evenings I bet emergency room docs feel otherwise).
  • Cases of bat-related rabies — EXTRAORDINARILY rare, often zero cases in a calendar year. The man from Barnstable was the fourth case in 2011 in the entire United States, the first rabies case in Massachusetts since 1935 — and first-ever bat-related case in the State.

Since most people with bats in the house aren’t seeking immunization, and since the “number needed to treat” to prevent a single case of rabies is estimated to be 2.7 million (!), the Canadians scrapped the recommendation that people who awaken to find a bat flying around their room get immunized.

And according to Larry, the World Health Organization now advocates a middle ground strategy of vaccine alone for minimal risk exposures. (US guidelines recommend rabies immune globulin as well.)

Time will tell whether these less aggressive approaches to rabies prevention will be the right move.

But I have a sneaking suspicion that sporadic cases will continue to occur — fortunately rarely — no matter what we do.

January 8th, 2012

Journal Club: In Early HIV Infection, Little Reason to Delay Therapy

Every experienced HIV clinician will recognize the following new-patient scenario:

  • At least one, but often several negative HIV antibody tests in the past, generally due to being in a “high risk” group.
  • Recent non-specific viral-type illness that, in hindsight, was undoubtedly acute HIV infection, undiagnosed.
  • Now completely recovered, but found to be newly HIV antibody positive.
  • Physical exam normal, CD4 500 or higher, HIV RNA in the moderate range (10-100K).

How should patients like these be managed? Specifically, should antiretroviral therapy be started, or should they be observed?

Over in Journal of Infectious Diseases, the so-called Setpoint study — a randomized strategy trial — investigated whether a 36-week period of treatment would delay the need to go on continuous HIV therapy, compared with observation. After 130 of a planned 150 patients were enrolled, a Data Safety Monitoring Board elected to stop the study due to this key finding:  “… the higher rate of progression to needing treatment in the Deferred Treatment group (50%) versus the Immediate Treatment (10%) group.”

Importantly, the findings would have been even stronger in favor of Immediate Treatment if more up-to-date CD4 thresholds (500 rather than 350) were used as a criterion to start therapy. (The study was designed in the mid 2000s.)

How do these results influence practice? As I’ve noted before, patients diagnosed with recently-acquired HIV infection should be counseled that even if treatment is deferred, there is a high likelihood they will need to start treatment relatively soon.

It’s also time to retire the “you may have 10 years before needing to go on therapy” counseling, something we might have been prone to do in the past to soften the blow of someone hearing that they’re HIV positive. This kind of delay is highly unlikely, and may be limited to the small fraction of patients who have very low HIV RNA and very high CD4s.

January 4th, 2012

How Does Herpes Treatment Trigger a Positive Test for Performance-Enhancing Drugs?

Here’s my guess on how many of this blog’s readers know the following “facts”:

  • Acyclovir and related drugs are used to treat herpes: nearly 100%
  • Ryan Braun, superstar left fielder for the Milwaukee Brewers, is facing a 50 game suspension for testing positive for elevated levels of a “banned substance”, most likely testosterone: 10%
  • Braun has disputed the results, stating that it’s a false-positive caused by treatment he’s receiving for a “private medical issue”: 1%
  • That medical issue is widely rumored to be herpes: 0.01%

Now I should mention that I am a huge Ryan Braun fan, not only because of his stellar play, and his nickname (“The Hebrew Hammer”, one Braun shares with Hammerin’ Hank Greenberg), but also because he bears an uncanny resemblance to my nephew.

But it’s that last bullet point I can’t quite figure out — treatment of herpes is incredibly safe. How in the world would it lead to an elevated level of testosterone?

Turns out, it doesn’t.

But a quick search of “acyclovir” and “testosterone”, plus a perusal of an actual book — the irreplacable The Use of Antibiotics — finds that there are some obscure animal studies suggesting that anti-herpes drugs could do the reverse, i.e., lower testosterone levels.

From the book:

Dose-related testicular atrophy and abnormalities of spermatogenesis were noted in mice, rats and dogs treated on repeated occasions with either famciclovir or penciclovir …

All of which leads me to the very speculative conclusion that some doctors could be providing testosterone supplementation to their patients receiving anti-herpes therapy.

Which is, frankly, a completely bogus indication, way more “out there” as a practice than the typical off-label use of approved medications.

But that’s the only way I can connect the dots here.

In other words, something’s not right — the test result, the diagnosis, the prescribing practice — we just don’t know what that is yet.

January 3rd, 2012

Prevnar Now Approved for Adults — But Should We Start Using It?

From the FDA (and thanks to Physician’s First Watch for reporting the news):

Prevnar 13, a pneumococcal 13-valent conjugate vaccine, was approved today by the U.S. Food and Drug Administration for people ages 50 years and older to prevent pneumonia and invasive disease caused by the bacterium, Streptococcus pneumoniae.

As shown in multiple studies, Prevnar has dramatically lowered the incidence of pneumococcal disease, both in immunized children and also non-immunized children and adults through “herd immunity.” The shift to infections with non-Prevnar covered serotypes has been of some concern, but clearly this vaccine has had a major beneficial effect — something harder to prove with the older, less immunogenic polysaccharide vaccine.

So should we use start using Prevnar in adults?

When I have difficult vaccination questions, I turn to several reliable sources:

  • My wife — pediatricians must give 100X (or more) vaccines than adult doctors
  • The Immunization Action Coalition, especially their “Ask the Experts” section
  • Howard Heller, my friend, ID Colleague, and Chief of Medicine at MIT Health Services, and adult immunization clinical expert

Howard kindly responded to my query this morning, and here’s his take:

We should still use the 23-valent pneumococcal vaccine (Pneumovax, PPS23) for adults until and unless the ACIP changes their recommendations. Although the conjugated vaccine induces higher antibody levels it has not yet been shown to decrease incidence of pneumonia, invasive disease or death. That study is underway. They will also be reviewing the data on the effect that Prevnar-13 in children has had on herd immunity and the prevalence of the various serotypes in invasive pneumococcal disease in adults. The advantage of the 23-valent vaccine is that it covers 10 serotypes that are not covered by PCV13. Stay tuned.

Thank you for that curbside, Howard — let me know if you have any questions about antiretroviral therapy!

December 28th, 2011

Why We Still Need HIV/ID Specialists

Over on Journal Watch AIDS Clinical Care, we periodically publish a tricky case — always drawn from clinical practice — then ask some experts how they would manage it, and why.

The most recent case pretty much has it all:

  • Multiple prior regimens
  • Multi-class drug resistance
  • Metabolic complications
  • Bad allergy history, one event nearly requiring hospitalization
  • Disfiguring lipoatrophy
  • History of treatment discontinuation

In fact, the case is so complicated that our Executive Editor said it made her “head hurt.” She’s just lucky the guy doesn’t have hepatitis C.

Fortunately, Graeme Moyle and Karam Mounzer kindly agreed to take it on. Given the complexity of the case, not surprisingly they came up with two different treatment approaches.

And patients like this are a reminder why, even in this era of single-pill-daily-for-HIV-treatment and 80-90% of patients in care virologically suppressed, we HIV/ID specialists still have a job.

December 24th, 2011

Making a List and Checking it Twice, Then Making Sure 052 is On It

How big a news story was HPTN 052, which demonstrated that HIV treatment reduced transmission by at least 96%?

(I like to emphasize that “at least” bit, since it’s likely that none of the study subjects with undetectable HIV RNA levels transmitted to their partners — the one case that did transmit did so before virologic suppression.)

Well, sources as disparate as Science and Time magazine both chose 052 for their “Top 10” in this year’s review of scientific breakthroughs. Science even put 052 as #1, something that you can bet we’ll have in common with this august periodical when Journal Watch AIDS Clinical Care publishes its own “Top Stories” next week.

But a Bronx Cheer out to Scientific American, which not only excluded 052, but then mentioned the following as a runner up:

…the report of a new target against HIV, in which a doorway to infection (the so-called CCR5-receptor on immune cells) is blocked.

CCR5 blockade a “new target”? That news is so 2002.

December 18th, 2011

Let’s Just Say I’m Glad the Grades Don’t Count

"Teacher, we are eager to learn."

A friend alerted me to this test of scientific literacy.

Give it a try — no google cheating — and let me know how you do.

And even though I got the first 5 questions right, my final score (to be disclosed in the comments, eventually) left little doubt that I was an English major in college.

Yeah, that’s my excuse.

December 14th, 2011

No HIV in Pepsi? Now THAT’S a Relief

How reassuring to be treated with the following news:

An SMS has been circulating that Pepsi products are contaminated with HIV but Permanis Sandilands Sdn Bhd has clarified that this is a hoax. Its marketing vice-president Hemalatha Ragavan said there was no truth to it. She urged people not to believe such claims.

I have a couple of thoughts about this breaking story.

First, we all know that texting — without other confirmation — is now the preferred current medium for obtaining important health information. And you can see how the text reads like the work of a highly-respected public health official:

for d next few days, do not drink any product from pepsi company like pepsi, tropicana juice, slice, 7up, coca cola, etc,,as a worker from the company has added his blood contaminated with HIV. watch NDtv …please 4ward this 2 every 1 u care about…..ok. Please note seriously

Second, the company issuing the denial — “Permanis Sandilands Sdn Bhd” — should think up a new slogan.  “Come on board, it’s time to be COOL, have FUN and DARE FOR MORE!” is not not going to cut it among hip Malaysians.

HIV Information: Author Paul Sax, M.D.

Paul E. Sax, MD

Contributing Editor

NEJM Journal Watch
Infectious Diseases

Biography | Disclosures | Summaries

Learn more about HIV and ID Observations.