An ongoing dialogue on HIV/AIDS, infectious diseases,
December 2nd, 2014
CROI 2016 Dates Announced — You Read That Right — and What Will We Be Talking About Then?
As any HIV/ID specialist knows, the Conference on Retroviruses and Opportunistic Infections, or CROI, is one of our very best (I think it’s the best) HIV scientific conferences, bringing together basic and clinical researchers for several days each winter in some cold, North American city for high-minded, scholarly pursuit.
But it has historically had a peculiar habit of releasing the dates of the upcoming conference unconscionably late, prompting all sorts of conspiracy theories and sleuthing, some of which I’ve playfully engaged in here.
No more — thanks to Donna Jacobsen from IAS-USA and the organizing committee, last year the CROI 2015 dates were announced before the 2014 conference.
And this year they’ve done even better:
Let the record show that we know the dates of CROI 2016 a full 449 days from now.
And what will the top news from that 2016 meeting be?
November 23rd, 2014
Five ID/HIV Things to be Grateful for this Holiday Season, 2014 Edition
Amidst outbreak hysterias, anti-vaccine imbecility, electronic medical record whining, and slug-related eosinophilia, I bring you this year’s version of the good news — the 2014 edition of Five ID/HIV Things to be Grateful for this Holiday Season, just in time for your holiday turkeys.
(Needless to say, the bird will be properly cooked to ensure it’s salmonella-free, with all cooking surfaces and utensils kept scrupulously free of cross-contamination. Gosh we’re an interesting bunch, aren’t we.)
So a humble and very sincere THANK YOU for the following, in rough order of impact:
- Interferon-free HCV treatment has finally arrived. With the December 2013 approval of sofosbuvir following closely after simeprevir, and the stellar results of the COSMOS study — limitations notwithstanding — we finally had an interferon-free regimen that worked (>90% cure!), and one which was blissfully free of significant side effects. Notably, the guidelines agreed, and this quickly became the most commonly used treatment for HCV genotype 1 in the United States. Then last month the news got even better with the approval of sofosbuvir/ledipasvir, along with a substantially greater body of data supporting its use and a a one-third lower price. Yes, the cost issues remain substantial, which is why I invited a colleague to join me at our Medical Grand Rounds recently to discuss it (you can watch here) — but the bottom line is that these advances in HCV treatment will transform the lives of literally millions world-wide.
- Many brave doctors and nurses are volunteering to assist in the Ebola relief effort. The health care workers who have chosen to go to Western Africa to help treat patients with Ebola virus disease deserve our profound thanks. Think about it: they are volunteering to leave home, volunteering to live in relatively poor surroundings, and most importantly, volunteering to put themselves at the greatest risk of contracting Ebola by caring for the sickest patients, all in the regions without sufficient “staff, stuff, systems, and space”. (That 4-s phrase is Paul Farmer-ism. I might have gotten the order wrong.) Needless to say, lunk-headed quarantine measures, imposed for political reasons or to fan the flames of fear, are not popular among ID doctors. Here’s an interview with Paul describing the Partners in Health relief efforts; you can guess his view on the governor of New Jersey.
- Treatment of HIV continues to look like the best way to prevent it from spreading. TAP might be best known as the abbreviation for Air Portugal, and the cardiologists might use it to describe transesophageal pacing, but to us ID/HIV specialists, it stands for “treatment as prevention”. The great news is that even 3-plus years after the publication of the 052 study, the data continue to show that effective HIV treatment all but eliminates transmission of the virus to others. An example: a study from CROI 2014 not only demonstrated that the rate of HIV transmission from on-treatment individuals to their uninfected partners was zero (caveat: there were confidence intervals), it also introduced many of us to the term “condomless sex.” And let’s face it, that kind of sex is here to stay, whether we like it or not!
- Fecal microbiota transplantation (FMT) not only works for recurrent C diff, but it is becoming the treatment of choice. Once all of us got over the “eww” factor (probably overrated to begin with), practitioners have increasingly made FMT available for patients with recurrent C diff — which is a very good thing because the treatment actually works. That’s more than we can say for these cobbled-together antibiotic tapering regimens, for which the supporting evidence was scant at best. The logistics of how best to go about delivering the healthy bacteria to these imbalanced colons still need sorting out, but one could envision something like these frozen poop pills — “poopsicles”, anyone? — as a prescription item in the not-too-distant future.
- Incentives for antibiotic development seem to be bearing fruit. In 2012, the Generating Antibiotic Incentives Now, or GAIN, provisions were signed into law with bipartisan (fancy that) support, extending by 5 years the exclusivity period for novel antimicrobials before generic competition. Whether this ultimately will be a good law or not remains to be seen, but it certainly is stimulating much-needed antibiotic development for drug-resistant bacteria. This year we saw three new agents active against gram positives, tedizolid, dalbavancin, and oritavancin; coming soon will be ceftazidime-avibactam and ceftolozane-tazobactam, both gram-negative cephalosporin-beta lactamase inhibitor combinations. Interesting overview of drugs in development here.
A few runners-up: The slow but certain end of the Western blot for HIV testing, conjugate pneumococcal immunization decreases childhood admissions for pneumonia, chikungunya cases might be declining in the Caribbean, and the CROI dates are now known well in advance (academic and vacation schedulers around the world thank you!).
What are you thankful for this late November 2014?
November 16th, 2014
Electronic Medical Records and the Demise of the Useful Medical Note
Electronic medical records (EMRs) are much on my mind, as last week at Medical Grand Rounds Robert (Bob) Wachter, chief of the medical service at UCSF, gave a brilliant talk on the unanticipated consequences of our move towards what he calls the “Digital Doctor.”
Bob has thought a lot about this issue, so much so that he’s about to publish a book on the topic. In his talk, after a brief history of how we got to where the vast majority of U.S. physicians use EMRs, he focused on three main consequences:
- The fact that doctors now interact as much (if not more) with screens as they do with patients — the “iPatient” phenomenon. The no eye contact problem. The lack of doctors on the medical wards, as we gravitate toward “work rooms” full of computers. You know how pediatricians sometimes get drawings from their school-age patients that include the doctor? He showed a remarkable example, in crayon of course, of a doctor facing away from the artist (the child), the MD staring at a computer screen and typing. From the book: “I’m guessing this one didn’t make it onto the doctor’s Wall of Fame.”
- The loss of interaction between doctors when the data are digital rather than something you can hold. Remember that brilliant radiologist who used to go over all chest films on your medical team? Now a radiologist may be reviewing films at home overnight, or in India, reports filed digitally and not requiring any human-to-human contact with the ordering doctor. Radiology rounds are slowly disappearing, along with the time for clinicians to pause — and think collectively — about what the images mean.
- The potential for automated systems to amplify medical errors. We’ve grown increasingly reliant on computers to help with decisions, for better and worse. In a taut, complex story involving a series of increasingly unlikely errors, he described how a child received a massive overdose of medication during hospitalization — all the indirect result of how a poorly designed systems can usurp clinician autonomy.
What he didn’t have time to cover (but does so in the book — he shared the excerpt with me), is the powerful effect EMRs have had on clinical notes.
It’s a fact that the note as means of communicating how the patient is doing has all but been destroyed. Notes even from the best clinicians routinely have the following features:
- A massive amount of repetition. Cut/paste phenomenon #1.
- “Required” elements that serve no clinical purpose. How useful is a lengthy review of systems? And isn’t a history-directed, targeted physical examination of far greater value than a comprehensive one “done” merely to meet higher billing criteria?
- Giant chunks of computer-generated data. Cut/paste phenomenon #2. It’s mostly lab and imaging results, with no interpretation of what the data mean.
- Factual errors. Cut/paste phenomenon #3. In the ambulatory record, one of my favorites is that some children never age: “Has three children, a son age 10, daughters ages 8 and 1” — which is then written unchanged in the social history over the next five years. Reminds me of The Simpsons — Bart, Lisa, and Maggie never age either. On the inpatients, we routinely see this: “ID consulted, considering pneumonia, UTI, C diff, disseminated fungal infection as cause for fevers” — then these same words are repeated for many days after some or all of these diagnoses have been ruled out.
- Sentences whose sole purpose is to avoid getting sued. You know ’em when you see ’em. They sound defensive, are depressing to read, and communicate no useful clinical information.
- Boilerplate text of highly dubious relevance to the individual case. During a mandatory “compliance” review of my notes (shudder — is there anything in modern medicine more painful?), I had someone suggest I add the following phrase to all of my notes: “More than 50% of this 30-minute visit was spent counseling the patient on the chronic nature of his/her condition, the rationale behind the laboratory tests ordered, the importance of taking medications directed, and the directions for making follow-up visits. Contact information provided, and patient’s questions answered.” The rationale? “You don’t do a procedure, so you need to improve the documentation of what you’re doing with your time.” Lovely.
The genesis of this problem, of course, is that the medical note is trying to do too many things at once. Previously a way of summarizing the clinical course of the patient, both for our own individual use and to communicate with other clinicians, it now has other masters with different motivations. Facilitated by EMRs, the note has subsequently evolved into a Jackson Pollock-like canvas of disjointed text, much of it of marginal or no clinical significance, with sections held together only loosely by the name and medical record number at the top of the page or screen.
Here’s a solution that will never happen — let’s have the medical note evolve even further, breaking it down into distinct sections based on their primary purpose. Imagine three tabs on the top of the note; you get to read only the one you want or need:
- Clinicians, here’s your section — it includes the stuff you really want to know, such as the history, exam, and lab/imaging results that matter (not all the labs/imaging, thank you), plus what the clinician writing the note thinks is going on, and what he/she plans to do.
- Billing compliance folks, read this part — it will have the required review of symptoms (most of them irrelevant), lengthy rubber-stamp documentation of counseling and education, and whatever other parts are required by whatever payor this patient has. And it will be inserted there by someone who’s not a doctor — or even better, by some automated bot — because successfully generating this kind of documentation is not why we went to medical school.
- Medicolegal guys, this is for you — lots of defensive phrases here, none of them of any clinical relevance, but they’re here just in case something untoward happens and the case ends up in court.
Have fun.
November 10th, 2014
Common Curbsides: The Tuberculin Skin Test and IGRA That Don’t Agree
Here’s one I’ve received twice in the past week, plus my answer.
As always, names/some details changed to protect patient confidentiality, plus my annotations in brackets/italics.
Hey Paul,
Quick question [Need I even comment about the “quick question” phrase, and how this unintentionally devalues what ID docs do? OK, I’ve commented, and yes I’m hypersensitive] — one of my patients, a 38-year-old woman from Serbia, is about to start biologics for rheumatoid arthritis [you can see this is going to be a latent tuberculosis testing question from miles away].
She’s not sure if she got BCG as a child [yep, called that one], so I did both [uh-oh] a PPD and sent a quantiferon gold [note this is not the crazy alphabetizing of the branded interferon gamma release assay (IGRA) products, which for some reason is “QuantiFERON®-TB Gold“ or the other one, which just goes with all-caps, “T-SPOT.TB”, and throws a period in the middle — jeeze, marketers]. The PPD is positive at 20 mm, but the quantiferon is negative [of course — otherwise there’s no question]. Her CXR is negative.
My conclusion is that she does not have TB and therefore does not need preventive therapy prior to starting biologics [that’s notable — putting your money down!]. Is that the correct conclusion?
I’m sure this is a very easy question [ah, not so easy after all] as you must get it all the time [second part is most certainly true].
Thank you very much sir [so formal! or maybe he was in the military] for your time.
Archie [not his real name, but it was the name of a dog we had growing up, a long-haired dachshund]
As noted above, nope, not so easy. Let’s consider the variables:
- She’s from a part of the world with a higher rate of TB than we have here. So the prior probability of latent TB is greater than if she was US-born, though it’s not as high as this.
- She’s about to get “biologics”, which by convention means some sort of expensive immunosuppressive drug, probably a TNF-inhibitor. These are of course great potentiators of TB, some worse than others.
- She may have received BCG, which can give you a false-positive tuberculin skin test. But this effect typically wanes over time, and even if she did get BCG, it’s probably not very effective in preventing adult TB.
- The sensitivity of the skin test vs IGRA is all but impossible to determine — because there is no gold standard for latent tuberculosis.
To summarize, the positive skin test could be a true positive, or could be a false positive from the (maybe) BCG. And the negative IGRA could be a true negative, or could be a false negative because it’s not 100% sensitive.
So what to do? Here was my answer:
The problem is that there is no gold standard — either one could be right. You might consider sending a T-SPOT, since it could be a bit more sensitive than the QF. But since biologics are strong potentiators of active TB, in general I’d recommend preventive therapy for a couple of months before she starts it (then completing a full course) since she’s from a part of the world with more TB than we have here.
PS: we had a dog named Archie when I was a kid.
So my question for you TB specialists out there — since this is such a common question, why doesn’t managing it appear in all the various guidelines and textbooks? Or am I missing it somewhere?
And speaking of dogs, it’s been a while since I showed a picture of Louie.
October 30th, 2014
Why the IPERGAY (Yes, That’s Its Name) Study Could Substantially Increase Use of PrEP
Yesterday, the French IPERGAY study of intermittent pre-exposure prophylaxis (PrEP) was stopped early by the Data Safety Monitoring Board, and for the best reason — the evidence demonstrating that it prevented HIV was overwhelming.
For those who read French, here’s the official announcement. (Scroll down for the English.) And for those who can’t believe the name, it stands for “Intervention Prophylactique pour Et avec les Gays”. Of course.
Here’s a short English version of the study: IPERGAY was a randomized trial of intermittent, “on demand” PrEP vs placebo done in high risk, HIV negative, men who have sex with men (MSM) in France and Canada. The specific strategy tested was:
- Two tablets of tenofovir/emtricitabine (Truvada) from 2-24 hours before sex
- One tablet 24 hours later
- Another tablet 24 hours after that one
So a total of 4 tablets over 3 days for episodic sexual activity, with an option for daily use for more frequent exposures.
We saw the pharmacokinetic data from IPERGAY in Melbourne, which showed that this strategy generated blood levels of tenofovir highly predictive of protection, and that appears to be borne out in these results. The full study detail are not yet available, but encouragingly they are reported to be better than iPrEx (the first study of PrEP in MSM). These results, along with the PROUD trial done in Britain — also stopped early for efficacy — substantially strengthen the data for PrEP in MSM.
So will the results increase the prescribing of PrEP? Even though the FDA has only approved tenofovir/FTC for daily use for prevention? I say it will, and here’s why:
- Patients have been asking about intermittent “on demand” dosing since the first day people were even thinking about PrEP.
- Even though iPrEx was a study of daily PrEP, it appears that many study subjects were taking it intermittently — and still were protected if they got drug levels correlating with 4 or more pills/week.
- Compared with daily dosing, this IPERGAY strategy will cost less.
- It will also reduce drug exposure, and hence likely toxicity.
- No one can say “IPERGAY” without smiling. Said with a French accent, of course.
Just like this film clip (it’s Monty Python week). Roll ’em!
(Hat tip to the excellent Myles Helfand for alerting me to the results.)
October 27th, 2014
IDSA Opposes Mandatory Quarantine of Healthcare Workers, and Andy Borowitz Is A Very Funny Person
From the Infectious Diseases Society of America (IDSA):
Strategies to limit the potential for Ebola virus disease transmission from returning healthcare and humanitarian aid workers as well as from other travelers should be based on the best available medical, scientific and epidemiological evidence; be proportional to the risk; balance the rights of individuals and the community; minimize unintended negative consequences; and minimize unnecessary use of limited resources. For these reasons:
IDSA does not support mandatory involuntary quarantine of asymptomatic healthcare workers returning from Ebola-affected areas. This approach carries unintended negative consequences without significant additional benefits.
The bolding is theirs, not mine, but I do agree.
And so, it appears, does Andy Borowitz, who has been spot-on in every one of his (fake) Ebola news pieces for The New Yorker. And today we got two!
First this:
Study: Fear of Ebola Highest Among People Who Did Not Pay Attention During Math and Science Classes
Then this:
And lest you think Borowitz limits his medical expertise to scary tropical viruses, his own personal experience with our healthcare system is about as accurate (and funny) a depiction of being a patient as you will see anywhere:
October 25th, 2014
What Makes An Ideal Applicant for a Fellowship in Infectious Diseases?
We’re at the tail end of the ID fellowship interview process, and am pleased to report we’ve seen some outstanding applicants.
They know that our field is the most interesting in medicine, and they view our recent “Epidemic of Epidemics” — to coin a phrase from John Bartlett to describe all this activity (Ebola, MERS, Enterovirus D68, etc.) — as not as a deterrent, but instead an important and fascinating challenge.
Face it: if it’s in the news these days, and it’s health related, there’s a good chance it’s an ID topic. Take a look at this, for example:
In that spirit, I thought I would share a recent email exchange with a former colleague:
Hi Paul,
I just started as program director for an internal medicine residency program in Illinois. I have been doing some career counseling with the residents, and have decided to email specialists I have known along the way with the following two questions about their field:
1. What are the characteristics of an excellent candidate for your fellowship?
2. How important is research experience? Bench vs. clinical?
Hope you’re well,
Craig
Here’s my response:
Hi Craig,
We look for the top clinical people, in particular those who relish the “great case” and love taking detailed patient histories (you know, does the patient have any pets, or has he/she been spelunking). They should definitely also enjoy bread-and-butter inpatient ID (which includes plenty of surgical/routine stuff as well as the fascinomas) and HIV and the complexities of transplant patients. It’s great when they express enthusiasm for the minutiae of microbiology (such as has Strep bovis changed its name?) as well as anti-infective agents (another cephalosporin — ceftolozane/tazobactam — is coming soon, am sure you’re thrilled). And they should want to be the local “expert”on all the newsworthy stuff that fills our days.
As for the research, it’s more important that they have a strong idea of what they would like to do. Yes if they have research experience, that’s a bonus, but it’s not required.
And they shouldn’t be going into ID for the $$$, or if they love to do procedures, because if they are, they are not very smart.
Nice hearing from you after all these years!
Paul
Sound about right? And what’s the story with Strep bovis anyway?
Speaking of pets and surgical infections, this one never gets old:
October 19th, 2014
Almost Filovirus-Free (That is, Ebola-Free) ID Link-o-Rama
If you’re an ID doctor right now, the filovirus of the moment Ebola is consuming a big chunk of all of your non-clinical time — and this is particularly true for those heavily involved in Infection Control, who are spending every waking hour responding to public hysteria, to various clinicians who seem to have all the answers, and to ever shifting federal, state, and regional guidelines. Thank you for doing this!
So as change of pace, I bring you this Almost Filovirus-Free ID Link-o-Rama, though this ever-challenging epidemic does make an appearance at the end.
- There’s been a bit of controversy on mandatory flu shots for certain healthcare workers at a certain New England hospital, whatever that could be. In response, I offer this brilliant Mark Crislip essay (it’s actually more of a tirade), which is republished annually by him and quoted by others, and falls easily into the must read now category — you will laugh, you will cry, and if you’re a health care provider you will nod your head with recognition many times, wishing you had the guts to write it yourself.
- Speaking of vaccines, this coverage of national immunization rates for children in kindergarten reminds us that while vaccine refusers can dangerously cluster within communities, overall the USA is still doing quite well — which is why our outbreaks of vaccine-preventable illnesses are comparably small compared with Western Europe. School regulations requiring vaccination before school entry is policy for the public good at its best — it’s what you’d expect an ID doctor married to a pediatrician to say, but so be it.
- Enterovirus 68 — which is now known as Enterovirus D68 — is feeling a bit left out of the Panic Virus Hysteria, but here’s some good news: there’s a faster, better test to diagnose the infection, which will no doubt give a much better sense of the full spectrum of disease, and whether it is truly linked to neurologic syndromes.
- Kudos to my friend, colleague, and co-ID fellow (don’t ask when) Libby Hohmann, whose study of … um … ingesting frozen poop pills (that’s the easiest way to say it) for C diff points to a future treatment of this nasty condition. Sure beats having a colonoscopy (prep and sedation) or a nasogastric tube (mega-yuck) for delivery of the required donor material.
- On the inpatient ID side, Staph aureus MICs may not matter after all. If you combine this result with the lack of clinical studies correlating vancomycin levels with outcome, and the fact that every ID fellow spends a big chunk of his/her energy chasing these levels until they are perfect, can we have some sanity on this vanco level issue please?
- And while we’re talking about our oh-so familiar foe Staph aureus, and in particular MRSA, this editorial suggests we reconsider patient isolation for this infection and for VRE. Seems it’s probably unnecessary — with several major medical centers (Cleveland Clinic, Dartmouth-Hitchcock Medical Center, Detroit Medical Centers, others) already stopping this practice. Boy that would be liberating.
- That editorial was part of a fun-packed JAMA issue that was completely devoted to Infectious Diseases, including a study showing that around half of all hospitalized patients receive at least one dose of an antibiotic. And the most commonly prescribed drug? Vancomycin, followed (in order) by ceftriaxone, piperacillin-tazobactam, then levofloxacin. I wonder what proportion of patients admitted to a medical service get a cardiac ECHO?
- Guess what? Measuring CD4 cell counts in stable HIV patients on suppressive treatment doesn’t influence treatment decisions. No surprise. The problem, of course, is convincing our patients that the test we’ve been doing for all these years is no longer relevant — easier said than done!
- OK, Filovirus time. The policy of treating all US Ebola virus disease patients in special biocontainment units has not as far as I can tell been formally enacted, but that’s what’s currently happening. There’s been some confusion about the capacity our system has for doing so, as not all the beds in all the units can be occupied simultaneously, but it seems that it’s a grand total of 11 beds — the NIH has 2, and Emory, Nebraska, and Montana each has 3.
Department of Shameless Self Promotion: You can now sign up and get notification about the latest post by putting your email address in the box on the right. Not saying you want to do this, just that you can.
And while we’re on the topic of self promotion, here’s a painfully funny takedown of egregious Facebook behavior. Don’t complain that you weren’t warned — because we’ve all been there, done that.
October 15th, 2014
Second U.S. Healthcare Worker with Ebola Further Underscores Urgent Need for Enhanced Preparedness — and Perhaps Designated Care Centers
If you’re like most of us, when you heard that a healthcare worker in Dallas had been diagnosed with Ebola virus disease, you assumed that the exposure occurred during his first visit to the hospital.
That is, before he was diagnosed with Ebola, and before infection precautions had been instituted.
But no, it happened after he was diagnosed, and isolated, and presumably when all the care providers were using infection prevention measures of some sort. The same is true for the second Dallas healthcare worker, and the nurse in Spain, and in none of these cases can a specific breach in precautions be definitively pinpointed as the cause.
Yes, the nurse’s union in Dallas is citing major problems with their protocols, and certainly there were issues in Spain as well. But regardless of what actually happened, these cases emphatically reinforce that safe care for Ebola virus disease is a monumental challenge. Which is why all of us ID doctors are on high alert for the time when such a case occurs, and why yesterday CDC stated they would send out an expert response team to any hospital that has a confirmed case — a decision that makes tons of sense.
I confess the magnitude of this infection control challenge did not fully strike me until last week — this is before the Dallas care providers were diagnosed — when I heard a fascinating, brilliantly clear plenary talk at IDWeek from Bruce Ribner, the doctor in charge of the Emory team that cared for two Ebola patients. If you have half an hour, I cannot recommend this presentation strongly enough.
There’s a shortened text summary here on the IDWeek website, and many of his slides can be downloaded here (they were used for a national teleconference yesterday).
A remaining question — should all Ebola virus disease patients be cared for in designated centers only? The CDC is actively considering this recommendation, which needless to say has huge ramifications for our healthcare system.
Your thoughts?
October 12th, 2014
Approval of Sofosbuvir/Ledipasvir Was Expected, but Still Is a Huge Advance
As expected, the FDA just approved the first single-pill treatment for hepatitis C genotype 1, a tablet containing 400 mg of sofosbuvir (SOF) and 90 mg of ledipasvir (LDV). For those not following this story closely, sofosbuvir is the pan-genotypic NRTI polymerase inhibitor approved last December to much rejoicing — and controversy about the price. Ledipasvir is the first HCV NS5A inhibitor, and is only available as part of this combination.
The brand name is “Harvoni”, which sounds a bit like an exotic offering on a menu that you need to ask your waiter to explain — “Ancho chile-rubbed Niman Ranch pork chop roasted in soy, ginger, and sesame, served with pan-sauted garlic kale, and garnished with corn and pinapple-harvoni salsa.”
But even though the approval was no surprise, and the brand name will (like all of them) take some getting used to, there’s no denying this is a huge step forward for HCV therapy. Let me list some of the reasons: