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An ongoing dialogue on HIV/AIDS, infectious diseases,
February 5th, 2017
The New England Journal of Medicine has published the first well-documented case of HIV pre-exposure prophylaxis (PrEP) failure despite good medication adherence.
We heard lots of this information at CROI last year, and again I’m impressed at the extraordinary degree of virologic investigation done on a case from clinical practice.
To refresh your memory, here are the critical details from the published case report and the supplementary appendix:
- A 43-year-old man began PrEP with TDF/FTC in April 2013, and had multiple negative 4th generation HIV screening tests over the next 21 months.
- Pharmacy refill records indicated excellent adherence. (Side note to young clinicians: Refill frequency is an amazingly powerful tool to monitor adherence.)
- Prior to diagnosis, he had multiple sexual exposures, including receptive anal intercourse without the use of condoms.
- A couple of weeks before his first positive HIV screening test (antigen positive, antibody negative — Day 0), he developed abdominal pain which waxed and waned over the next 3 weeks. A CT scan demonstrated thickening of the sigmoid colon, ascending colon and rectum. Endoscopy revealed erythematous patches of the sigmoid colon.
- Adherence was confirmed by analysis of a plasma sample obtained on Day 0 revealing tenofovir concentrations consistent with recently taking the drug.
- HIV RNA peaked at 28,000, and became undetectable with the addition of boosted-darunavir and raltegravir.
- His viral isolate had extensive multi-class resistance, including to FTC (M184V), TDF (multiple thymidine-associated mutations), NNRTIs (Y181C), and first-generation integrase inhibitors (92Q).
- He’s now virologically suppressed on DRV/c, RPV, and DTG.
The supplementary appendix has an excellent figure of the timeline, which I’ve pasted below:
So what can we learn from this single case?
- PrEP is very effective, but it’s not 100% protective. I don’t think clinicians are claiming 100% effectiveness, but PrEP-takers may be hearing this from various “experts”, or may be misunderstanding the data.
- Transmitted drug resistance will weaken PrEP. Although all of the mutations in the case are to drugs not in the TDF/FTC combination — except M184V — the multiple TAMs could have weakened TDF through cross resistance. Furthermore, FTC could have been transmitted, or alternatively selected by period of viral replication after viremia developed. The source patient’s virus was not available for sequencing, unfortunately.
- The symptoms of acute HIV infection are highly variable. The supplement to the case reports states, “The patient did not have classic symptoms of acute HIV seroconversion”, which is true — but he did have GI symptoms, which are quite common in acute HIV. We need to remember this variability when following patients on PrEP.
- The monitoring strategy recommended by the CDC in the guidelines should be followed. Although it might seem like overkill to monitor for HIV and other STIs every 3 months while receiving PrEP, remember that only those at highest risk for getting HIV should be receiving PrEP to begin with. Clinicians may choose to recommend more frequent monitoring if clinically warranted.
- Integrase resistance is rare in clinical practice, and transmitted integrase resistance is even less common. While some might interpret this case report to indicate a need for baseline integrase testing for newly diagnosed individuals, the detection of transmitted integrase resistance in most studies of newly diagnosed patients is less than 1%, and often 0%. Notably, the transmitted virus was still sensitive to dolutegravir (I’d interpret the genotype as fully susceptible).
Ok, that’s what I learned. Provides a cautionary note to those both prescribing and receiving PrEP, one further reinforced by this additional case report of PrEP failure presented at a recent conference.
As for tonight’s game, below is what I’m going to watch, and here’s why!
January 29th, 2017
This was not a happy or comfortable weekend for ID doctors, given our predilection for inclusiveness, non-judgmental care, global health, and that “safety net” idea that seems to us such an intrinsic part of being a good doctor.
Exclusion of foreigners? Why, we ask, would you do that? People from other countries are our friends, our colleagues, and our patients. Many of our favorite patients, I might add, since they might bring with them exotic, challenging, and treatable problems that are right up our alley.
Furthermore, to overstate the obvious, most of us living here in the USA are not that far removed from immigration ourselves.
Fidencio Saldana — he’s a cardiologist, the Dean of Students at Harvard Medical School, and the child of Mexican immigrants — gave medical Grand Rounds at our hospital recently.
He recounted what it was like being a medical student here, and how out of place he sometimes felt. He then movingly described how was made to feel welcome by hearing from one of our senior doctors, Marshall Wolf:
Hey relax. My parents were immigrants too. You belong here.
That was two weeks ago, a brief aside made at a lecture, yet I have thought of it frequently since, especially this weekend.
And this morning, glum and discouraged by recent events, I needed some distraction.
So I turned on the television at 6AM and watched two of the most extraordinary athletes in the world, Roger Federer of Switzerland and Rafael Nadal of Spain, play the fifth and deciding set of tennis at the Australian Open in Melbourne, Australia.
The crowd was cheering, and hanging on every point, and no doubt millions of others all over the world were doing what I was doing — watching and marveling and feeling a sense of global togetherness for this extraordinary event.
And here’s the best part. After Federer won the match, a grueling 5-set affair that lasted over 3 hours, he graciously said:
Tennis is a tough sport, there are no draws. But if there was I’d be happy to share it with Rafa tonight.
Share. No gloating. No petty rivalries. No cheating. No distortion of facts. These are the best players in the world, competing at the highest level for hours, and they can still get along like friends even in the most intense setting imaginable.
You got that?
January 22nd, 2017
Welcome to Fun with Old Medical Images!
Here’s how it works: You’ll see a series of images — old, strange, and perplexing — and each will have a caption that I have created for you at no extra cost.
Accustomed to high-quality and clinically relevant information from your NEJM Journal Watch contributors, you will laugh happily at the contrast between that solid content and this silly exercise, forgetting for a moment the complicated and sometimes contentious world we live in.
See, this will be therapeutic.
Off we go. Here’s the first one:
Poor Perkins! I’m sure he’s also wondering why his doctors didn’t give him a pillow.
That was fun. Ready for #2?
So many promising drugs fail during clinical trials due to side effects! At least dreaming of lamb chops is safer than QT prolongation.
Now, onto #3:
Such stillness in that room! And who’s the uniformed man in the upper right? Is he a scribe?
We’re on a roll! Here’s #4:
The laughs keep coming, so let’s go on to #5:
Here the key question — did medical insurance in mid-19th century France cover the cost of Uber for housecalls? I did a quick search — fascinating result.
Should we finish with a neat half-dozen? Why not, here’s #6:
Nothing but fun at this ophthalmologist’s office! Eye appointments always last too long, so why not get checked for glaucoma and get a bit more stylish at the same time?
Thank you for taking this tour of Old Medical Images, I hope you enjoyed it as much as I did.
Next time, we’ll go back to our usual programming.
January 16th, 2017
- A Las Vegas woman died after infection with a pan-resistant strain of Klebsiella. While CDC receives many isolates of carbapenem-resistant enterobacteriaceae (CRE), 80% are susceptible to at least one aminoglycoside and 90% to tigecycline — not this one, which retained susceptibility only to fosfomycin (a drug not available in this country for systemic use). One critical detail in this case was her multiple recent hospitalizations in India related to a right femur fracture and osteomyelitis of the right femur and hip. As with this case of metronidazole-resistant Bacteroides, the travel appears to be the critical exposure history. Question for those who practice in a Travel Clinic — do you now counsel patients about their risks of acquiring highly resistant organisms during travel to certain countries? Seems this risk is particularly high with travel to Southern Asia — probably higher than many of the more exotic conditions that get more attention.
- A man experienced a delayed diagnosis of TB meningitis due to a false-positive multiplex PCR. A 75-year-old man presented with mental status changes, and the BioFire FilmArray on the CSF was positive for HSV-1. Herpes encephalitis, case closed, right? However, the ultimate diagnosis was tuberculous meningitis, and the HSV-1 was not confirmed by additional PCR testing using another FDA-approved assay. Of course in hindsight, it seems clear that this wasn’t clinically consistent with HSV-1 encephalitis, FilmArray result notwithstanding — onset of confusion and speech difficulties was gradual, not acute; an MRI showed no parenchymal abnormalities, unusual in someone with HSV-1 encephalitis of this duration and severity; there was a neutrophilic pleocytosis and markedly elevated CSF protein; he developed hydrocephalus. Individually, several of these could rarely be seen with HSV-1 encephalitis, but together along with his clinical worsening they appropriately raised the concern that the diagnosis was incorrect. Of course hindsight is 20-20, and the most important message in this case is not to succumb to “premature closure” if the clinical picture does not fit the lab test result — an especially important lesson with new testing modalities.
Now, to enlist your support for vaccines, for which there is the highest level of evidence for efficacy and safety. At the kind invitation of Carey Goldberg, the skillful editor of WBUR’s CommonHealth blog, I wrote a piece about the possible appointment of Robert F. Kennedy Jr. by Trump to lead a commission on vaccine safety and scientific integrity.
Kennedy, you may be aware, has a lengthy history of pushing anti-vaccine propaganda.
To you, loyal readers of an ID/HIV blog, I am going to state with 99.9% confidence that you will agree with my views — but please read the piece anyway. This debate about the risks and benefits of childhood immunizations is still (amazingly), a thing — just read the comments if you can stand it — and we need all the support we can get.
But I have a query. Here’s the NPR Facebook page on the piece, with one section highlighted for discussion:
Not sure exactly what they meant by “oddly delightful”, but I’m pretty sure it’s better than the converse — “delightfully odd.”
Happy MLK Day.
January 8th, 2017
A few medicine and family practice residency programs around the country have a dedicated track that focuses on HIV care. Though the programs naturally differ somewhat in structure — here are two examples from University of Washington and Yale — they generally involve placing the resident into an HIV clinic for their longitudinal outpatient experience.
We don’t have such a program here, though I’ve been asked about it several times over the years. I can certainly think of advantages and disadvantages to this specialized track.
And since we’re in the midst of residency interview season — plenty of young, bright people wandering around the hospital in dark suits they might not wear again for a couple of years — it seems a good time to consider the issue.
On the plus side for the HIV track:
- Residents with a stated interest in HIV care can get a head start on their career choice.
- There’s a projected shortage of HIV clinicians, and this training will help provide a capable and interested group of young doctors in the field. Residents can skip specialty training in ID and transition right to primary care with a panel of HIV patients.
- Under current training standards, program directors report a high proportion of internal medicine residency graduates are not adequately trained to provide primary HIV care.
- People with HIV are more likely to be poor, from minority or other traditionally marginalized communities (gay men or people with addiction), and having more clinicians sensitive to their needs certainly is a plus.
On the minus side:
- A focused HIV track arguably limits both the breadth of patient experiences and the ambulatory clinical challenges for the resident. Shouldn’t residents get as broad an education as possible at this early stage of their training? This is especially important if they change their minds and choose to do something else.
- If there’s going to be an HIV track, why aren’t there specialty tracks for other diseases? How about more common conditions, such as the primary care needs of cancer survivors, or people with mental illness, or diabetes? Or to choose a couple of problems with comparable numbers in the USA to HIV — how about adults with congenital heart disease, or those with lupus?
- Since so many patients with HIV today are completely stable from the HIV perspective, a dedicated HIV track isn’t necessary. The focus of residency should be learning how to manage problems of aging (hypertension, diabetes, COPD, cancer screening) since these are the most important issues for many HIV patients anyway. Data are emerging that a primary care/specialty collaboration works well — here’s a good recent paper evaluating this issue.
- Doctors who want to manage the most complex HIV issues — multi-class resistance, knotty metabolic abnormalities, opportunistic infections, challenging drug interactions — should do additional subspecialty training Infectious Diseases. In most clinical settings, these situations would prompt a specialty referral regardless of how a resident was trained.
I’m not going to pretend to have the answer to this one. That’s why there’s a poll, and the comments section!
January 1st, 2017
A lot of these “Best of …” or “Top Stories in …” lists have already been published, as they seem to be appearing earlier and earlier each year. Pretty soon we’ll start reading them around the same time they sell Halloween Candy — and that’s just too early, sorry.
Now this list, however, appears just as 2016 is in the books, all 365 days accounted for and scrupulously reviewed. And I chose five because, well, five follows the rules.
(I just finished a block on service and can’t resist linking that post, since the rules came up literally every day.)
Of course by choosing only 5, I’ve necessarily had to leave off some big HIV stories this year in research, clinical care, or policy, so feel free to enter your top story in the comments section.
Drum roll, please.
Number 5. TAF/FTC Approved.
With approval this year of co-formulated TAF/FTC, we now have the ideal NRTI pair to use in treatment of, well, pretty much everyone. Yes, we already had TAF/FTC as part of the single tablet treatments of TAF/FTC/RPV and TAF/FTC/EVG/c, but those aren’t appropriate for all patients — both must be taken with food, RPV has high viral load and low CD4 restrictions, and EVG/c has a long list of drug interactions. The availability of TAF/FTC provides greater flexibility when, for example, you want to use it with a different 3rd drug — dolutegravir, or raltegravir, or yes even efavirenz — or as part of a more complex salvage regimen, where it’s generally given with DRV/r.
Number 4. HIV cure research inches forward.
Admittedly, we’re still stuck on 1 person cured — the famous Timothy Ray Brown, he of the CCR5-negative stem cell transplant (and cute dog). But that “n of 1” has led to extensive pre-clinical and clinical research on HIV cure, with lots of very smart people working on the problem. Here’s one notable (and surprising) example — antibodies directed against alpha4/beta7 integrin given to SIV-infected primates led to sustained viral suppression after stopping ART. This finding led to rapid initiation of a human study at the NIH using the drug anti-alpha4/beta7 drug vedolizumab, which is already approved by FDA. One caveat on all this research — HIV cure studies are notorious click-bait, as demonstrated here.
Number 3. First large HIV vaccine study in 7 years starts in South Africa.
It’s called HVTN 702, and it will enroll 5400 seronegative people in South Africa, arguably the country in greatest need of an HIV vaccine. Participants will be randomized to receive either placebo or a vaccine series modeled after the RV144 clinical trial in Thailand. The HVTN 702 strategy, however, modifies the vaccine to provide greater and more sustained immunogenecity than RV144, and has been further adapted to the HIV subtype that predominates in southern Africa. Fingers crossed!
Number 2. PrEP gains traction — but it isn’t perfect.
When TDF/FTC for pre-exposure prophylaxis (PrEP) was approved in 2012, I thought it was going to remain a niche intervention, rarely requested by patients or ordered by clinicians. However, since the presentation of the PROUD and IPERGAY studies in early 2014, and the release of guidelines by the CDC, use of PrEP has taken off — around 80,000 people in the USA are now receiving PrEP, a more than 700% increase since 2012. Most of the use, not surprisingly, is in MSM from affluent urban areas. Two cautionary notes: First, the highest risk patients — young MSM of color, especially in the south — aren’t getting it nearly enough; second, PrEP isn’t perfect, with two failures (here and here) despite good adherence, likely due to transmission of NRTI-resistant strains.
Number 1. Treatment as prevention really really REALLY works.
Did I make that clear enough? Publication of two major papers proved this point: 1) The final results of HPTN 052 showed ZERO transmissions from an HIV-infected study subject to his seronegative partner if the blood HIV RNA was undetectable, and; 2) The PARTNERS study, which explicitly recruited serodiscordant couples not using condoms, again demonstrated ZERO transmissions. We all thought that ART would be effective in preventing HIV transmission — but the degree of protection is way beyond what any of us could have hoped. It’s this effect that’s probably leading to a decline in new HIV diagnoses in certain major cities that have a high proportion of patients on treatment, such as San Francisco, New York, and London.
Happy New Year, everyone!
And in honor of the setting for HVTN 702 (see #3 above), here’s 2016’s most popular Youtube video in South Africa.
(Thanks to NPR.org for the video reference.)
December 18th, 2016
- Holiday parties.
- Travel plans — specifically, should we go with DEET or picaridin?
- Lots of high-carb, high-calorie foods stealing blood from our brains. Maybe too much eggnog or punch doing the same thing.
- Kids on vacation, with their demands for sustenance, adult supervision, and entertainment.
- Many critical work support people already away, with out-of-office messages implying that they’re not reading their email (but you know that they are).
Even our pets are distracted. After a crazy weekend of New England weather, starting with bitter cold, then a day of wet snow, and now a Spring-like thaw, Boston dogs and cats who ventured outside today are in bad need of bath.
(And yes, that was just an excuse to show off that magnificent picture of Louie. Click on it for full effect, I dare you.)
Plus, you have the distraction of our latest ID Cartoon Caption Contest, which generated so many outstanding entries that our powerful advanced humor algorithm was unable to limit the finalists to just three candidates this time. Even after we tweaked the settings, the powerful supercomputer churning through the entries kept overheating. We almost had to cancel today’s post and substitute a lengthy rumination on whether you should say Mycobacterium avium complex (MAC) or Mycobacterium avium-intracellulare (MAI).
(Short answer: the former.)
So here’s the cartoon, plus the top four choices. Vote now before 2016 is no more!
(Drawing by Anne Sax.)
December 11th, 2016
About a million years ago — in other words, probably sometime during my ID fellowship — I asked transplant ID guru Bob Rubin how various ID guidelines came together, including one on antifungal therapy he had just led.
“You lock a bunch of experts in a hotel conference room,” he said. “Provide them plenty of food and coffee. Then you hide the key until they come up with something, especially if there’s a deadline .”
Having participated on a couple of guidelines committees, I can attest that the process has changed just a bit since Bob provided me that memorable story. Conference calls, web-based presentations, and numerous shared documents with extensive “track changes” peppered throughout now dominate the process, along with frequent reminders about grading both the strength of the recommendations and the quality of evidence.
And, since we’re ID doctors, we of course try to outdo each other in obsessive attention to detail — emphasis on obsessive. While everyone makes a big noise about editing and shortening the final document, if that means eliminating one key reference, tell that to its champion — especially if they authored or co-authored the paper. It’s going in!
On the topic of guidelines, you might have noticed that the Infectious Diseases Society of America (IDSA) has been on quite a roll over the past year. They’ve been churning out new guidelines at a blistering pace, often in collaboration with other medical societies. So here’s a look back on IDSA’s hard work over the past 12 months, each one highlighted with at least one notable and/or interesting recommendation, and also (just for bragging rights) the number of references (all thoroughly read, no doubt):
- Candidiasis. Last updated in 2009, these revised guidelines cover diagnosis, prevention, and treatment. A selected key recommendation: An echinocandin is recommended as initial therapy, with transition to fluconazole if the isolate is susceptible. Number of references: 560 — impressive!
- Antibiotic Stewardship. The first of its kind! A selected key recommendation: Rapid viral testing for respiratory pathogens is recommended to reduce the use of inappropriate antibiotics. Number of references: 225 — you have to think this will grow in the next iteration.
- Aspergillosis. Prevention, diagnosis, and treatment of this difficult-to-treat opportunistic infection. A selected key recommendation: Serum and bronchoalveolar lavage galactomannan can accurately diagnose invasive aspergillosis in high risk patients; the panel disagreed about using PCR. Number of references: 655! Wow, that might be hard to beat.
- Hospital-acquired and ventilator-associated pneumonia. Retires the term “health-care associated pneumonia”, often abbreviated (and spoken) as “H-CAP” — will be hard for many to break that habit. A selected key recommendation: Duration of therapy should be 7-days (follows the rules!), not 8-15. Number of references: 364. Middle of the pack.
- Coccidioidomycosis. What a mouthful that fungal disease is, which must be why most people just say “cocci.” A selected key recommendation (actually two this time): No antifungal treatment for an asymptomatic pulmonary nodule (not even a bit of fluconazole?), while duration of azole therapy for coccidioides meningitis is lifelong. Number of references: 219 — a relatively “low” number, maybe because cocci’s geographic distribution isn’t very wide. Nah, 219 references is still a lot.
- Treatment of drug-susceptible tuberculosis. The winner for the most number of organizations involved in developing and endorsing these guidelines — I counted 9 (just read the start of the abstract). A selected key recommendation: Initial adjunctive corticosteroid therapy should not be routinely used in patients with tuberculous pericarditis. Number of references: 531 — would be top of the pack if you added the other TB Guidelines (which are next).
- Diagnosis of tuberculosis. First update on this topic in 17 years, so long overdue. A selected key recommendation: Use an interferon gamma release assay (IGRA) to assess for latent TB in place of the tuberculin skin test (TST) in most clinical settings. I’m ok with that! Number of references: 241 — hey, it’s just diagnosis after all.
- Leishmaniasis. Diagnosis and treatment of cutaneous, mucocutaneous, and visceral disease. A selected key recommendation: Use a reference laboratory to perform culture and PCR in an effort to identify the infecting parasite to the species level, which may have implications for management. Number of references: 503, which exceeds the number of cases of leishmaniasis I have seen by 498.
That’s 8 Guidelines, and a total of 3,298 references. Hard at work, IDSA!
Of course no listing of IDSA Guidelines these days is complete without the invaluable HCV guidelines, which I’ve praised (and use) often. They’ve changed so frequently since their inception that they have their own special site, and aren’t really “published” anywhere else — at least not in a traditional medical journal. On the plus side, this allows the HCV Guidelines greater flexibility, with modifications on an as-needed basis (three times in 2016 alone) for important changes in the field — a nod to the DHHS HIV Guidelines, which have a similar structure. On the minus side, there’s no real peer review, and I’m sure some of the writers of the guidelines (especially those seeking academic promotion) wouldn’t mind a byline discoverable in PubMed.
And they don’t number their references, so someone else has to count. Kind of like guessing the number of pennies in a big jar to win a prize.
Finally, here are some bears playing with a pink balloon. Just because.
December 4th, 2016
A selection of ID/HIV questions that have been dogging me over the past year, some longer:
- Why is there no reliable, readily available PCR diagnostic test for malaria? Seems especially ironic since the one for babesia has become so commonly used. Does the Binax antigen test make it unnecessary?
- Why aren’t we actively recommending Zika testing for couples who return from endemic areas and are interested in conceiving? A negative test would make a low-likelihood but serious outcome (congenital Zika) even less likely. They could still wait the recommended six months if they want.
- What is the right abbreviation for Pneumocystis pneumonia? Is it “PCP” (PneumoCystis pneumonia) or “PJP” (Pneumocystis jirovecii pneumonia)? Have heard smart people use both; I prefer the former.
- Once there are more manufacturers of generic daptomycin and the price drops, how long before it’s used more than vancomycin? If we never have to monitor vancomycin levels again, there should be a small celebration.
- In the big new HIV vaccine study just starting, how many participants will also be receiving PrEP? Here’s the study design of HVTN 702, and PrEP clearly is allowed. I suspect it won’t be available to most of the participants, otherwise it could make it hard to discern whether the vaccine actually works.
- Does anyone really know the full meningococcal vaccination recommendations without looking them up? For the 99% of us who don’t, here they are. This is an old bugaboo, inspired by the new recommendation to give meningococcal immunization to all HIV patients.
- Could the headlines be any more misleading about how many patients contracted HIV or HCV from the dentist who used his own equipment? Here’s an example — you have to read it carefully to make sure you see the “May” in there. But gotta sell papers/get clicks (and I just contributed to the latter).
- Speaking of, is this the headline of the year? I think we have a winner, folks — “GOVERNMENT DRONES WILL SHOOT VACCINATED M&MS AT PRAIRIE DOGS.” The disease, for the record, is the “sylvatic plague.” You have to read the full story to believe it. And just wait for the anti-vaxxers to protest.
- If primary care clinicians had a rapid diagnostic test that could tell patients definitively that they had a specific viral respiratory tract infection, would this decrease the use of outpatient antibiotics? They could say, “Mr. Smith, your test came back, and you have rhinovirus.” I say “Yes it will”; my colleague Jeff Linder (a primary care internist who studies antibiotic overuse) is skeptical.
- Will broadly neutralizing antibodies (“bNAbs”) ever have a role in HIV treatment? Not based on this study. Admittedly it’s early in bNAb research, but to date I’m not getting the bNAb enthusiasm.
- We have penicillin G, and penicillin V, but what about the other letters? Hat tip to John Cafardi for this one.
- Wouldn’t it be useful if ID doctors had some formal training in wound management? Big gap for many (most?) of us.
- What percentage of non-occupational HIV post-exposure prophylaxis courses are unnecessary? I’m estimating 99.9994%, but that train seems to have left the station, with no going back.
- Why did the new makers of crofelemer change the name from (the absurdly wonderful) Fulyzaq to (the less remarkable) Mytesi? And here’s an artist’s rendition of a Mytesi, in case you were sad about the extinction of Fulyzaq.
- In Lyme-endemic areas, why is there no recommendation to give a single dose of antibiotics to children with tick bites? Odd that we use this strategy in essentially all adults, and almost no children — it’s as if we were applying drinking-age criteria to this completely unrelated issue.
- Why is a CSF exam recommended in all patients with optic or otic syphilis? Treatment is the same (IV penicillin) regardless of the results. Have been asking this question for years.
- What fraction of HIV viral load tests that come back “VIRAL RNA DETECTED BUT BELOW THE QUANTIFIABLE RANGE OF THE ASSAY” are clinically important? Boy that must be rare. The ratio of (Emotionally important to patient)/(Clinically important to patient) must be nearly infinite.
- What’s it like to have an oral carbapenem? Someone from Japan might know.
Ok, time for a couple of quick non-ID ones:
- When will the Washington Redskins change their offensive name? Or the Cleveland Indians get rid of their unfunny mascot?
- When will the torture of choosing a password be replaced by something easier and more reliable? Here’s one recent example. Arrghh.
Hey, it’s National Influenza Vaccination Week! Check your party schedule carefully.