An ongoing dialogue on HIV/AIDS, infectious diseases,
March 22nd, 2020
Quiet Hospital Zone
Academic medical centers right now would provide visitors — if they were permitted — a strange experience.
Usually buzzing with clinical and research activity, with incessant human interactions in hallways, on rounds, at the bedside, in conference rooms, our hospitals are now eerily quiet — and very, very, tense.
Minus the intensive care units, the “special pathogen units” (or whatever name assigned to them), the emergency room — the rest of the place is practically silent.
Elective ambulatory care has basically shut down. Same for elective surgeries.
Scheduled for screening colonoscopy? Cancelled.
Annual mole check with your dermatologist? Rescheduled for 3 months (at least) from now. Hernia repair? Sorry.
Follow-up with your nurse practitioner about that new blood pressure medication? Virtual visit — better get that home blood pressure monitor out from the closet.
The inpatient floors have, as usual, patients with acute medical and surgical problems — but discharges occur expeditiously, with signs at the hospital entrance prohibiting visitors. This is no place anyone wants to linger. The hospital census is way down.
As for conferences, they are all but done. Medical grand rounds, clinical case conferences, morbidity and mortality, resident report — all cancelled, or converted to Zoom, or Webex, or GoToMeeting, or Skype, or whatever your platform may be.
The cafeteria still serves food, but there’s no self-serve anything, a tricky pivot for an enterprise that usually offers many buffet choices. Forget the salad bar. A long-term kitchen employee — Pat, she’s wonderful — wears a mask and kindly hands you your cup of soup, using plastic gloves and plenty of distancing.
No groups congregate at the tables — which are pushed to the side of the room. Don’t sit here.
The cashiers have a wary look on their face — please don’t hand me cash — but to their credit, are as friendly as ever.
Quiet. Hospital Zone.
March 16th, 2020
Difficult Times — Meaning No CROI Really Rapid Review 2020
In a usual year, right about now, I’d be obsessed with two things:
- What were the most practice-changing studies presented at the Conference on Retroviruses and Opportunistic Infections, or CROI? I’d want to summarize those for a patented, copyright-protected, check-with-my-lawyer-before-copying, Really Rapid Review©®.
- How will the upcoming baseball season play out? Most readers here don’t care, I concede. Oh well, we all have our enthusiasms.
But this isn’t a usual year, especially not for us specialists in Infectious Diseases.
Baseball is on hold for now, thank you coronavirus — they say two weeks, but everyone knows it will be longer. Who knows.
As for CROI? Due to some remarkable sleight of hand, at the last minute it became a virtual meeting, with research and plenaries presented online. The planners moderated the sessions in place right here in Boston — but no one attended live.
I thought about writing a Really Rapid Review©® on this electronic CROI.
But I was so distracted by COVID-19 activities that it was tricky. (Ok. Impossible.) Today I concluded that the product wouldn’t meet the high standards of those who read this site regularly, for which you have my sincere gratitude.
Meanwhile, you can take a look at this isolated citation from the conference. I do think it is the most important practice-changing study from CROI 2020 — how often do we see randomized clinical trials in pregnant women with HIV?
(HARDLY EVER. There, I answered.)
It’s called IMPAACT 2010. And with the disclosure that I’m a (relatively unimportant) co-investigator on the study, and obviously some disappointment that it didn’t get the attention it deserved, here’s a take-home message — DTG + TAF/FTC may well be the best regimen for treatment-naive pregnant women.
Important, practice-changing RCT presented a #CROI2020 on Rx of HIV in pregnancy. Take-homes:
– DTG superior to EFV in viral suppression
– TAF/FTC+DTG best for adverse pregnancy outcomes
– Weight gain most with TAF/FTC+DTG; closest to rec wt changes @IMPAACTNetwork pic.twitter.com/6mNWstFbVX— Paul Sax (@PaulSaxMD) March 11, 2020
Meanwhile, if you want to know how your fellow ID doc feels right now, take it away Adi:
Medical professionals internally right now pic.twitter.com/vYlABMUycv
— Adi (@IDdocAdi) March 16, 2020
Thank you for your patience. And take care of yourself during this difficult time.
March 8th, 2020
As Testing Ramps Up, Diagnoses of Coronavirus Disease in the U.S. Will Soon Increase Substantially — How Will We Respond?
Brace yourself. As coronavirus disease (COVID-19) occurs at multiple locations around the United States, the number of confirmed cases here is about to increase big time.
There are two reasons:
- New infections
- More testing
Believe it or not, despite statements by certain politicians, COVID-19 tests still cannot be ordered by any clinician who believes it should be done. In many parts of the country — including, as of today, Massachusetts — a local health department continues to be the only place to get the test. These state labs have limited resources, and hence must offer the test only to those who have a clear exposure, or have a severe respiratory illness without other obvious cause.
That’s about to change. Two of the largest commercial labs in the country, LabCorp and Quest, announced that they have tests ready to go.
Plus, multiple academic medical centers plan to modify their existing molecular diagnostic assays by adding the coronavirus genetic sequence as a target. This will enable testing to be done rapidly “in house” at hospitals that see the highest volume of critically ill and immunocompromised patients.
And not a moment too soon. By all objective measures, our testing has been woefully inadequate, meaning that the reported number of diagnosed COVID-19 cases are the proverbial tip of the iceberg — an iceberg of the pre-climate change magnitude.
Consider — today’s report shows 484 cases reported with 20 deaths. Remember that these tests were done mostly on the sickest people. That’s why our mortality rate is so high at 4.1%.
By contrast, consider South Korea, which already has widespread disease and an aggressive testing policy (they have apparently done over 140,000 tests). They have diagnosed 7,314 COVID-19 cases, with 50 deaths, for an estimated mortality rate of 0.6%.
If we apply that 0.6% mortality rate to the 20 deaths we’ve had here, this would mean there are already around 3,000 cases in the United States. We just haven’t been testing enough to find them.
(Apologies to epidemiologists for the crude estimates. Hey, math is hard.)
There are several ways we could — as clinicians, scientists, media, public — react to this surge of cases that will inevitably dominate the headlines in the coming weeks.
On the negative side is panic, which will bring with it further hoarding behavior, conspiracy theories, and unproductive accusations. On this last one, I’d like to emphasize what I posted here about the people I know who work at CDC and the department of public health — they are not to blame:
Agree. The people I know who have worked at @CDCgov and at @MassDPH have been hard-working, mission-driven, and science-based individuals who want to do the right thing. They must be given the resources they need. https://t.co/iukkqLkRMb
— Paul Sax (@PaulSaxMD) March 7, 2020
Another terrible reaction will be to suppress the information.“I like the numbers being where they are” is not an effective mitigation strategy — a strategy which will be critical to prevent the overburdening our healthcare system (see figure).
What I’m hoping for?
Let’s welcome the accurate data, even though the numbers will sound scary. It’s time for expansive tests for COVID-19, even introducing them as soon as possible on our multiplex respiratory virus testing platforms.
Such information will give us a much better sense of the spectrum of the illness here, as well as the risk factors both for COVID-19 acquisition and severe disease. It will also allow us to institute more sensible infection control policies, to allocate resources where the disease is most prevalent, and to construct viable strategies to turn the tide against the epidemic.
When Knowledge is Power confronts Ignorance is Bliss during a public health emergency, give us the first one every time.
March 6th, 2020
CROI 2020 Will Be a “Virtual Meeting” After All — Plus, What Scares Me (and Doesn’t) About Coronavirus
This just in:
BREAKING NEWS: #CROI2020 will be a virtual meeting this year! Thanks to @IAS_USA @DonnaJacobsen and all CROI leadership for wrestling with this difficult decision and putting public health first. https://t.co/KPmJ66x7GL
— Melanie Thompson (@drmt) March 6, 2020
If you’re a frequent reader of this blog, you might have read here just minutes ago that it was going ahead after all — with a discussion about how difficult it must have been for the organizers to make the decision.
Never mind. Kudos to all of them for remaining nimble in this uncertain time.
As for the coronavirus situation, there are some things I truly fear — and others, not so much.
I was asked to write about them on WBUR’s CommonHealth. Many thanks to Carey Goldberg for this idea, and coming up with the excellent title.
February 25th, 2020
First Week on Service, with One-a-Day ID Learning Units
There is almost always something to be learned from every new patient.
It might be buried somewhere in the history, or the physical, or the lab tests, or the micro, or the imaging — but the odds are excellent that, with enough rumination, you’ll find it.
I can’t remember now who taught me this important fact, or even if it was ever explicitly stated to me. Quite possibly it was just implied — or personified in action — by some really smart, impressive clinical mentor. Someone skilled in finding that nugget of learning in every case.
It might have been my legendary residency program director; or the World’s Greatest Chief Medical Resident (I’m still missing her, sadly); or the brilliant Chief of ID during my fellowship; or the most intuitive ID clinician on the planet.
(FYI, that last guy remains an invaluable resource on tough cases.)
Regardless, these ID Learning Units are out there. And here are seven — one-a-day — from my first week on the inpatient ID consult service:
1. Cystic neutrophilic granulomatous mastitis. You’ll have an “a-ha” moment the first time you see this strange and challenging entity.
Day #1: Cystic neutrophilic granulomatous mastitis (CNGM) is a chronic inflammatory process, associated with corynebacterium spp. (Causal?) Optimal management remains unclear–generally involves combination of abx and corticosteroids. @Yijia_89 https://t.co/RjeerNHSb6
— Paul Sax (@PaulSaxMD) February 19, 2020
2. Consider pulmonary arteriovenous malformations when encountering a brain abscess, especially if there are no other obvious risk factors.
Day #2: Pulmonary arteriovenous malformations are a risk factor for bacterial brain abscess; some have a history of recurrent nosebleeds, with visible mucocutaneous telangiectasias on exam. Suggests all brain abscess pts should be screened for PAVM. https://t.co/KAtOECbJOn
— Paul Sax (@PaulSaxMD) February 20, 2020
3. Chronic meningitis — must be one of the most difficult diagnoses in all of ID.
Day #3: Chronic meningitis is CSF pleocytosis that persists for at least 4 wks without spontaneous resolution. ID, autoimmune, and neoplastic processes may be causative; up to 30% no Dx. Next gen sequencing may help. @Yijia_89 @rose_m_olson https://t.co/ZAbUMFOljW
— Paul Sax (@PaulSaxMD) February 21, 2020
4. A convenient cefazolin dosing strategy in hemodialysis — thanks to Dr. Chris Bland, who pointed out this even better study. A real game-changer for inpatient ID consult services everywhere.
Day #4: Cefazolin dosed post-hemodialysis is an ideal strategy for treating MSSA infections in patients with ESRD, obviating the need for a PICC line or other catheter. Excellent PK; good outcome in this small clinical study of bacteremia. https://t.co/nfRca4S49t
— Paul Sax (@PaulSaxMD) February 22, 2020
5. With cutaneous lesions that may be zoster, PCR is the diagnostic test of choice — much better than both culture (which lacks sensitivity) and direct fluorescent antibody (DFA) testing, which is highly dependent on getting enough cells.
Day #5: PCR is the diagnostic test of choice for cutaneous VZV, greatly surpassing viral culture in sensitivity (and also much less operator dependent than DFA). Of course in many cases, clinical diagnosis is sufficient! https://t.co/pt3z80fecA
— Paul Sax (@PaulSaxMD) February 23, 2020
6. You know those patients with a positive syphilis screening test, a positive confirmatory test, but a negative RPR? Well, as we’ve discussed before, they’re quite unlikely to have neurosyphilis.
Day #6: In a study of 265 CSF exams, not a single case of neurosyphilis was diagnosed among those whose blood VDRL was negative. Similar study from Hopkins with RPR. h/t Khalil Ghanem https://t.co/lkyu3sNiKL pic.twitter.com/ptk0ScztFy
— Paul Sax (@PaulSaxMD) February 24, 2020
7. When scanning your HIV patient’s historical genotypes, if you find Y188L, that eliminates the entire NNRTI class of drugs. It’s also naturally present in all HIV-2 isolates.
Day #7: Universal resistance of HIV-2 to NNRTIs is due to the Y188L polymorphism, which appears in all HIV-2 isolates. (Similarly, when seen in HIV-1, Y188L confers resistance to all NNRTIs, including doravirine, +/- etravirine.) @Yijia_89 https://t.co/tpeGG1Upgn
— Paul Sax (@PaulSaxMD) February 25, 2020
February 17th, 2020
Short-Course Treatment of Latent TB, Combination Therapy for Staph Bacteremia, Adult Vaccine Guidelines, Novel Antifungals, and Others — A Non-COVID-19 ID Link-o-Rama
There’s so much out there right now on COVID-19 (the disease) and SARS-CoV-2 (the virus) that the other ID news gets crowded out.
Which means it’s time for non-COVID-19 ID/HIV Link-o-Rama! I haven’t done one of these in a while, so there’s plenty of material in the vaults yearning to be free.
- The CDC now recommends short-course, rifamycin-based, 3- or 4-month latent TB infection treatments as preferred over 9 months of isoniazid. Completely agree, as 3 or 4 months seems so much shorter than 9 months. Important reminder — watch for rifampin-related drug interactions! Will the 1 month of rifapentine plus isoniazid regimen be in the next version of these guidelines?
- Among patients with MRSA bacteremia, addition of an antistaphylococcal β-lactam to standard antibiotic therapy with vancomycin or daptomycin did not overall improve outcomes. While persistent bacteremia was numerically reduced with combination therapy, vancomycin plus an antistaphylococcal penicillin led to a higher rate of renal injury, prompting the DSMB to stop the study early. This safety issue was not observed with cefazolin, so vancomycin plus cefazolin is still being studied in a separate trial. Excellent summary from the lead author Steven Tong here.
- Ceftaroline plus daptomycin combination therapy may reduce mortality in patients with MRSA bacteremia. This retrospective, matched cohort study supplements favorable findings on this combination from an earlier, small, randomized trial. Some appropriately cautionary commentary from the lead author Erin McReary here. Unfortunately, it does not appear that a randomized study of this combination is in the works due to the cost of the drugs and lack of interest from the manufacturers. Let’s continue the staph bacteremia theme but move on to MSSA with …
- Cefazolin and ertapenem appear to rapidly clear persistent MSSA bacteremia. This uncontrolled study describes 11 patients for whom this combination treatment quickly cleared blood cultures. The authors postulate that ertapenem “rescues” the relatively attenuated activity of cefazolin against MSSA, noting that certain microenvironments (such as bacterial endocarditis vegetations) might make this reduced activity clinically relevant. That’s enough Staph bacteremia for now!
- The latest DHHS HIV guidelines have added dolutegravir (DTG) plus lamivudine (3TC) as a recommended initial regimen. This is the first time a two-drug regimen has garnered this status. Appropriately, there is accompanying cautionary language about excluding baseline HIV RNA > 500,000, chronic hepatitis B, and transmitted M184V. With the encouraging data on this highly effective two-drug regimen, I ask — what’s the purpose of abacavir/3TC/DTG, which is also still listed?
- The TANGO study showed that people with viral suppression on tenofovir alafenamide (TAF)-based treatments can safely switch to DTG/3TC. Switch strategies will likey account for most of the use of this DTG/3TC regimen, since for initial treatment, it’s still easier to go with TAF/FTC/BIC or TAF/FTC plus DTG (no need to know baseline viral load, resistance, or hepatitis B status). And another dance-named study — SALSA — will expand this switch population to anyone who doesn’t have resistance to either 3TC or DTG (no baseline TAF regimen required). No reason why the results of SALSA will be any different than TANGO, but of course surprising things do happen. And no, I don’t know what either of these acronyms stands for.
- The cost of antiretroviral therapy in the United States is high — and increasing faster than the rate of inflation. In 2012, the yearly average wholesale price for recommended initial regimens was $25,000 to $35,000, increasing to $36,000 to $48,000 in 2018. While hardly anyone pays this full price due to insurance, the AIDS Drug Assistance Program (ADAP), patient assistance programs, and other funding mechanisms, even paying part represents real hardship for some patients — especially concerning since high out-of-pocket costs negatively impact adherence.
- Immunization for zoster may reduce the risk of stroke. In a review of Medicare data, receipt of the live zoster vaccine was associated with a 20% reduction in the risk of stroke for those younger than 80. Note that the data analyzed preceded the availability of the recombinant zoster vaccine, which is more effective in preventing shingles than the live version. Since zoster is a potential trigger of stroke, would we see an even greater decline in stroke incidence with the newer vaccine? A compelling additional motivation for immunization.
- Roughly $42 million was spent responding to measles outbreaks in 2019 alone. In addition to the huge cost of controlling these outbreaks, there is also the opportunity cost for public health departments and their staff — who have plenty of other work to do. So annoying.
- Another state has a bill to eliminate “religious” exemptions for vaccines. Strongly support these bills! These non-medical exemptions for children are particularly insidious, as clinicians out of respect may not want to question patient preferences based on religious beliefs. But the reality is that no mainstream religion actually prohibits vaccinations, which is why I put “religious” in quotes.
- The Advisory Committee on Immunization Practices (ACIP) released its 2020 Adult Immunization Schedule. As anticipated, they formally endorse some changes hinted at previously — notably no longer recommending pneumococcal 13-valent conjugate vaccine (PCV-13) for all adults older than 65 (“consider” based on preference), and supporting the HPV vaccine up to age 45 if patients have ongoing risk for new infection.
- Approximately 8% of mycoplasma isolates in the United States have evidence of resistance to macrolides. Difficult to estimate the clinical implications of this resistance, since we rarely isolate mycoplasma in clinical practice and such testing is only available in research laboratories. Regardless, fluoroquinolones and doxycycline likely retain activity, along with the recently approved drug lefamulin — an antibiotic I still haven’t had the opportunity (or cause) to use.
- Here’s a mega-review of investigational antifungal agents. Rezafungin, ibrexafungerp, olorofim, fosmanogepix, et. al. — the gang’s all here! An incredibly useful paper, especially for those of us not actively involved in antifungal research.
- In a retrospective, multicenter, cohort study done in the VA system, empiric anti-MRSA therapy for patients hospitalized for pneumonia was associated with worse clinical outcomes — even in those at risk for MRSA. By using some serious statistical gymnastics, the investigators examined data from 89,000 admissions to emulate a clinical trial result. Can you say “inverse probability of treatment–weighted propensity score analysis using generalized estimating equation regression” and explain it, please? Still, it’s another cautionary note about unnecessary broad-spectrum therapy and a real boost to antimicrobial stewardship efforts to stop empiric vancomycin.
- Dr. Aditya Shah, an ID Fellow at Mayo Clinic, continues to make us laugh. How about this one from last week?
When the attending supervises the procedure you are doing #stewardmeme https://t.co/WqEIaJ2W8O
— Adi (@IDdocAdi) February 16, 2020
Adi was kind enough to join me on an OFID podcast to discuss what motivates and inspires him to post these memes — highly recommended!
February 9th, 2020
Should Medical Subspecialists Attend on the General Medical Service?
As I’ve written about many times on this site, one of the highlights of the year for me is when I attend on the medical service — something I’ve been doing pretty much forever.
There’s a wonderful learning exchange that goes on, with my knowledge of ID being repaid in kind by the others on the team — interns, residents, nurses, pharmacists, other attendings — who bring me up to date on current general medicine outside of ID.
(Including the acronyms. Yikes!)
I tried to capture this flow of information by commenting on this highly amusing post by Mayo Clinic’s Dr. Adi Shah — and hence confess was taken aback by this comment from Dr. Stephen Shafran, an ID doctor from Canada:
https://twitter.com/ShafranStephen/status/1215526965697896449?s=20
This is an important perspective, one which we subspecialists should examine carefully. How can we ensure that the care and supervision we provide be as safe as that done by a generalist?
This concern has been on my mind the past few weeks, prompting posting of this poll:
Hey #medtwitter, picking up on a classic @IDdocAdi meme from earlier this year, I ask this question — is it ok for medical subspecialists to attend on a general medical service? Why or why not?
— Paul Sax (@PaulSaxMD) February 8, 2020
While the results are reassuring, this is hardly scientific — clearly many of the people who participated are ID specialists themselves, and probably many of them also attend on general medicine.
So, where are there actual data? I searched for studies on clinical outcomes for generalist versus subspecialist inpatient attending — and came up with very little.
One study from a single academic medical center suggested that hospitalists had more efficient use of resources (shorter length of stay and costs) than rheumatologists and endocrinologists, but clinical outcomes (readmissions, mortality) were similar. So, is it really unsafe?
As for the trainee experience, this group from UCSF argued strongly that having subspecialists as medical attendings greatly enriches their learning, and might motivate residents to pursue a given subspecialty as a career.
In the absence of definitive information, allow me to list certain strategies that I hope mitigate the safety issues Dr. Shafran raises.
- Those of us subspecialists who choose to do inpatient medicine generally maintain certification in Internal Medicine as well as our specialty.
- It’s very much a self-selected population of subspecialists who choose to do general medicine.
- The subspecialists well-represented on general medicine services have, in their day-to-day activities, a substantial amount of general medicine in their practice — both inpatient and outpatient. There’s a reason you won’t see many subspecialist attendings on medicine who spend most of their time inserting coronary stents or doing ERCPs.
- Obtaining consults on cases outside of one’s comfort zone is encouraged, and never considered a sign of weakness.
One other thing, perhaps specific to our hospital, is the structure of our medical team. The rotations typically pair us subspecialists with hospitalists or outpatient generalists. While only one doctor can be the attending of record for a given patient, the team has two attendings, both hearing about all cases on rounds. More on this team structure here.
After the above exchange occurred on Twitter, I received the following kind email from Dr. Badar Patel, one of our interns:
The experience I’ve had with subspecialists serving as our general medical attendings have all been extremely positive, and I don’t believe we’ve had safety issues as the Twitter thread would suggest. I am interested in medical education and would love to be involved if an opportunity to study this in a formal manner were to come up.
For a start, he’s created a survey about this issue, and already sent it to our house staff.
If you’re in clinical medicine, we’d be thrilled if you would take it as well — here’s the link. All responses are anonymous. We plan to write up the results in a future perspective piece.
And who knows, maybe we’ll learn something! After all, we all have the same goals — better care for our patients, and a better learning experience for our trainees.
Thoughts, comments, and opinions on this topic most welcome!
February 2nd, 2020
A Coronavirus ID Link-o-Rama, Because I’m Not Watching the Super Bowl
With so much of the ID-related news out there dominated by the novel coronavirus (2019-nCoV, hard to type) outbreak, it seems appropriate to collect some of the more interesting or useful findings in this busy past week.
Think of it as an ID Link-o-Rama — Special Novel Coronavirus Edition.
As with last week’s post, an important caveat — the outbreak continues to evolve rapidly, and data quickly become out of date. All are encouraged to check in with the excellent guidance and information on the CDC, WHO, and IDSA sites (among others), all of which are updated regularly.
On to the links:
- The mean incubation period of novel coronavirus disease after contact with an active case is around 5 days. The 95% confidence interval around that estimate is 4.1 to 7.0 days. Importantly, the onset of symptoms 2 weeks or more after exposure appears very unlikely. These data should dispel circulating rumors that this virus has a much longer incubation period than other coronaviruses — in fact, it appears quite similar (Figure 3).
- This case cluster demonstrates coronavirus can spread before the onset of symptoms. However, as in most infectious diseases, symptomatic cases are probably more contagious — usually because people with symptoms have a higher viral burden. While the findings in this report are of concern, the true contribution of asymptomatic spread of the virus in the present outbreak remains unknown. [Update: The “asymptomatic” person may have had symptoms after all. Additional details summarized here.]
- The New York Times has posted a widely cited figure comparing mortality and contagiousness of coronavirus with other infectious diseases. Current estimates are 3% mortality and transmission number (R0) between 1.5 and 3.5. It’s an impressive graphic (modeled on this one) that puts the infection into perspective. Importantly, note the log scale of the vertical axis in the Times figure, which prompted this revision:
This is one of those “please don’t judge me for making this horror” graphs that I’ve just thrown together with possibly the least reliable underlying data (hence extensive caveats in caption). All available on github, please scrutinise and send improvements pic.twitter.com/vtU3bUFDzH
— Isaac Florence (@IsaacATFlorence) January 31, 2020
- Here’s a clear explanation why the estimated mortality will likely change — for the better — as we gain greater understanding of the disease. Severe cases tend to dominate reports early in an outbreak; only later, when diagnostic tests and surveillance improves, will we understand how many mild (and even asymptomatic) cases occur. Remember when West Nile virus first appeared in North America? It was initially terrifying — yet we now know that 80% of people who acquire this infection do so without any symptoms whatsoever, and fewer than 1% develop encephalitis.
- Wonderful perspective from Dr. Elizabeth Rosenthal offering her advice on how to avoid coronavirus. Wash your hands frequently. Yep, that’s it — plus a few other things that fall squarely into the “common sense” category. The piece includes interesting anecdotes from when she covered SARS in 2002-3 as a journalist, living in China with her family.
- This online calculator estimates the effectiveness of screening travelers to detect people who have 2019-nCoV. You can move the sliders around on parameters such as incubation period, proportion who have fever, and R0 (transmissibility), among others. Not surprisingly, those most likely to be detected have both fever and a reported epidemiologic risk.
- Some patients with coronavirus disease have already received antiviral therapy with drugs demonstrating in vitro activity against the virus. In this report, a woman received lopinavir/ritonavir (along with oseltamivir). In another case, doctors received permission for compassionate use of the experimental drug remdesivir. Both patients improved — but obviously in these anecdotal cases, we don’t know if they would have improved anyway. A Chinese clinical trials registry cites at least one planned study. My virologist colleague Dr Jonathan Li summarized some of the background data in this thread.
- How did this novel coronavirus first spread to humans? This is critical information — not only for this outbreak, but also for prevention of future zoonotic infections. Excellent summary of ongoing work in this area.
- A pre-print reported that the novel coronavirus had insertions that bore an “uncanny” resemblance to HIV gp120 and Gag. This finding (later withdrawn) triggered a momentary spike in conspiracy theories that would be excellent evidence for the benefits of scientific peer review — which happened in this case anyway, only not in the usual way. For a good takedown, read this analysis.
- Many have tried to put the coronavirus outbreak in perspective by citing this year’s flu season. Here’s the brilliant opening from the linked piece:
The rapidly spreading virus has closed schools in Knoxville, Tenn., cut blood donations to dangerous levels in Cleveland and prompted limits on hospital visitors in Wilson, N.C. More ominously, it has infected as many as 26 million people in the United States in just four months, killing up to 25,000 so far.
In other words, a difficult but not extraordinary flu season in the United States …
So yes — get your flu shot! Listen to Dr. Stephenson!
#Influenza and #coronavirus are the same problem. It’s not a competition over which virus is the scariest. They are circulating at the same time which complicates diagnosis and treatment and add together to stress our health care systems. Flu #vaccine helps *both* outbreaks.
— Katy Stephenson, MD, MPH (@k_stephensonMD) February 1, 2020
As for the title of this post …
Nope.https://t.co/ElJH4KIpvp via @sciam
— Paul Sax (@PaulSaxMD) February 2, 2020
January 26th, 2020
Uncertainties Notwithstanding, Pace of Scientific Discovery in Coronavirus Outbreak Is Breathtakingly, Impressively Fast
The current novel coronavirus outbreak due to 2019-nCoV and SARS from 2002–3 share many features, including:
- Both are coronaviruses, genetically distinct from those that had caused infection in humans previously (most of which led to cold-like illnesses)
- First cases recognized in China, with subsequent international spread
- Source an animal reservoir — likely bats for both of them
- Both cause severe lower respiratory illness
- Documented person-to-person spread, including nosocomial transmission to healthcare workers
What direction 2019-nCoV goes from here remains uncertain, as the current outbreak is rapidly evolving. Despite the extensive press conferences and commentaries from public health officials, microbiologists, and specialists in Infectious Disease — most of them quite thoughtful — the uncertainty will no doubt lead to isolated overstatements of both alarm at one extreme and reassurance at the other.
For a good primer on the current situation, The New England Journal of Medicine and JAMA both weighed in with last week with excellent perspectives.
Uncertainties notwithstanding, I can assuredly say one thing is vastly different this time compared with SARS — the pace of scientific discovery and communication, especially on the molecular level, is breathtakingly fast.
Think about it — less than 2 weeks after the first reported cases (December 31), researchers released the genetic sequence of the virus in its entirety. It’s now available in GenBank.
We already have a diagnostic test being used by our CDC and, internationally, other public health laboratories; this paper describes how such a test might work.
After isolation of the virus, a pre-print demonstrated its affinity for the human ACE2 receptor, which is present predominantly in lower respiratory tract cells. A second scientific group confirmed this finding.
A description of the clinical syndrome can be found here; the incubation period in this family cluster was 3–6 days, though may average 10–14 days; and investigators estimate its contagiousness (R0) — always a dynamic number, especially early in an outbreak — in this report.
Several mention ongoing plans to test drugs with in vitro activity, including approved (lopinavir/ritonavir, interferon) and investigational (remdesivir) agents. Tony Fauci says time from virus discovery to a vaccine in Phase 1 studies could be 3 months — fast!
All of this is quite amazing — and would not have been possible during the SARS outbreak.
Another thing different from 2002 is this was pre-Social Media — which, for all the bad things associated with the specific platform of Twitter, on the plus side it remains an extraordinarily efficient way to transmit and summarize data, at least when it’s done by a thoughtful individual.
Here’s Exhibit A, a must-read thread from Dr. Muge Cevik, an ID doctor in Britain. Thank you!
THREAD
As the #nCoV2019 outbreak continues, a lot of data emerging in real-time & being rapidly disseminated.I compiled the available data (in no particular order) to have a better understanding of #nCoV2019 & will update the list as more info become available. #IDTwitter
— Muge Cevik (@mugecevik) January 25, 2020
Meanwhile, a plea to our media outlets — can we get expert opinion from true experts on viral infections, public health, and policy? Good grief, will Dr. Gwyneth Paltrow be next?
January 20th, 2020
Telemedicine, eConsults, and Other Remote ID Clinical Services Make So Much Sense — Why Isn’t Everyone Doing it?
The ID group at Mayo Clinic just published a small but important study on the use of remote ID telemedicine consults for hospitals that have no ID services on-site.
The consults were “asynchronous”, meaning that the ID consultants at the main hospital finished them within 24 hours — they didn’t have to respond immediately. Importantly, all the institutions shared the same electronic medical record, so the consultants could review notes, lab results, and other tests.
Comparing 100 cases who had “eConsults” with 300 historic controls, the investigators found that the cases with ID eConsults had a substantially better clinical outcome — a 70% (!!!) lower 30-day mortality.
These results didn’t come from some Magic Dust available only to survivors of the bitter cold Minnesota winters — the primary interventions recommended by the consultants included very straightforward (for an ID doctor) advice, such as antibiotic changes, antibiotic duration change, antibiotic deescalation, additional laboratory testing, and consultation with services other than infectious diseases.
The authors acknowledge the important limitations of the study, primarily the fact that the non-randomized design leaves it open to unmeasured confounders influencing the outcome.
Furthermore, since they utilized historical controls, changes in practice could have led to the improved outcomes, not the eConsults themselves.
Still, limitations notwithstanding, let’s imagine the effect isn’t quite this large — it’s still very impressive. As noted by Dr. Saurab Patel, the upper bound of the 95% confidence interval on the reduction in mortality was 30%! People who study health care quality and outcomes would take that any day of the week, thank you very much.
Furthermore, satisfaction among the clinicians ordering the consults was extremely high. Indeed, we find the same thing at our hospital, where we provide eConsults to our primary care clinicians and specialists for non-urgent questions that arise during outpatient care. I attended a meeting of primary care providers on the use of eConsults, and the enthusiasm for this service was off-the-charts high — they love them!
So based on a study like this and our experience, every clinical ID Division in academic medical centers and every ID private practice must be lining up to provide eConsults, telemedicine, or other forms of remote advice, right?
Well, not quite:
Hey #IDTwitter, do you currently do "eConsults" or provide telemedicine services for patients you have never seen for a face-to-face visit? Can be for other clinicians, or directly to patients, or both. Take the poll, then explain why or why not. Thanks!
— Paul Sax (@PaulSaxMD) January 19, 2020
Only just over half the respondents do these kinds of consults currently, even though arguably the non-procedural and cognitive-based aspects of ID practice fit perfectly into this remote care model.
In the Discussion section of the paper, the authors cite two major reasons why a substantial fraction of ID doctors don’t do these sort of consultations:
Cost and technical challenges are major barriers to the widespread adoption of telemedicine.
Let’s take the second of these first, the technical challenges.
If you don’t have the same electronic medical record as your consulters, providing this kind of formal consultative service would be difficult, if not impossible. What we ID doctors do best is carefully review the relevant history, laboratory, and imaging data, and make recommendations from synthesizing this information. It’s critical that this review is as reliable as possible — especially since confirming details by talking to the patient may not be possible.
(Reminder: ID doctors take the best histories. Thank you.)
Another challenge is institution-specific credentialing. Even affiliated hospitals in the same healthcare system may have different criteria and systems for credentialing their clinicians. This makes doing a remote consult on inpatients at other facilities far from straightforward — and doing it across state lines might actually be prohibited if the consultant is not licensed in that state.
Now on to the thorniest issue, which is cost. It’s not simply that we’re too busy. If these kinds of clinical services were valued highly enough, we would make time in our schedules to do them, pushing out lower value activities.
In the responses to my poll, the most enthusiastic endorsements of remote consultations come from settings where American-style fee-for-service compensation plays comparably minor role (if that) in a doctor’s salary. Europe, Canada, and here in the U.S., the VA — you get the idea. Says Dr. Ilan Schwartz from Canada:
We cover a catchment area from central Alberta to NW Territories — a geographic area almost 1/3 that of Canada! For some assessments I prefer ability to examine the patient, but for others, telehealth consult is in their best interest. Also sometimes roads are really icy, and if I can spare patients both the inconvenience and the risk of shleping to Edmonton, I will.
No surprise here! What Ilan does in Western Canada makes all kinds of sense, reminiscent of the ECHO research project using telemedicine to treat hepatitis C in remote areas of New Mexico.
But in a differently funded healthcare system — ours — where payment is overwhelmingly based on racking up face-to-face encounters and procedures, the time spent doing eConsults and telemedicine is time not spent in revenue-generating patient care.
And in most practices, eConsults score a big fat zero when it comes to RVUs, that loathsome metric for measuring a U.S. doctor’s “productivity”.
Time for that to change!
Because doing what’s best for patient care should motivate how we spend our clinical time, not racking up RVUs.