Move over London, here comes Flint

Epidemiologists are drawn to London for its role in the etiological tale or origins of their field. It's hard to discount the importance of John Snow's investigation of the Broad Street cholera outbreak of 1854 and its role in advancing public health. Even when looking at the simple case-control study, many are first taught about the methodology using Doll and Hill's famous 1947 study linking smoking and lung cancer, which was completed in London hospitals.

Digging even deeper, we see that the initial case-control study was thought to be Janet Lane-Claypon's report comparing 500 women with and 500 women without breast cancer admitted to London and Glasgow hospitals published in 1926. However, as in many historical investigations, claims of "firsts" in epidemiology are often overturned upon further review. And while London will always have a special place in epidemiologists' hearts, it turns out that another city needs to be recognized; a city we often ignore...

For those of you not familiar with US or automotive history, Flint Michigan is best known as the birthplace of General Motors and like many industrial midwest towns, it has fallen on hard times. Beside GM, it is also the birthplace of Sandra Bernhard, Bob Eubanks, Michael Moore, Grand Funk Railroad, Glen Rice and, apparently, the Case-Control Study.

In a paper published in the December issue of the American Journal of Epidemiology, Alfredo Morabia uncovered an old case-control study by George Ramsey buried in a 1925 issue of the American Journal of Hygiene. In July 1924, there were 41 cases of Scarlet Fever; a high rate in the summer. A dairy inspector soon learned of an employee at an ice cream plant who had continued to work even after he developed a sore throat and rash (presenteeism!!). However, an investigation of the case patients with scarlet fever did not identify a specific risk factor, including ingestion of ice cream from a single dairy. Then the investigation was "supplemented" by histories taken from 117 controls, who did not have scarlet fever. The questioning revealed very few differences between cases and controls except that cases with scarlet fever were much more like to frequently eat ice cream (60%) compared to controls without scarlet fever (24%). When the investigators looked specifically where cases bought their ice cream, they identified a specific factory as the culprit (see Figure below).  It turned out that Factory A was where the sick worker had worked! Further testing revealed hemolytic streptococcus in ice cream samples from Factory A.

The Discussion section of this recent paper points out that most of the advancements in epidemiological methods occurred in cancer and heart disease. Apparently, there was not another case-control study used in infectious disease epidemiology until 1940. What is amazing is that it appears the Dr. Ramsey and the Michigan Department of Health hit upon the case-control design all by themselves. The paper concludes: "Flint, Michigan, the cradle of General Motors and of recognized labor unions in the United States, appears to have also been a birthplace of case-control studies."  Merry Christmas Flint - hold your heads up high!

image source: missourireview.com

Administrative data for HAI surveillance: fuhgeddaboudit!

There's a new paper in Clinical Infectious Diseases by Eli and company that is the definitive treatise on the use of administrative claims data for healthcare associated infection surveillance. I have never been a fan of using coded data for this purpose for two reasons: (1) it shifts the important work of surveillance from trained infection preventionists to medical records abstractors who are not trained in surveillance methodology and who are limited by their ability to only review notes written by physicians; and (2) while it's a quick, cheap and dirty method, as Eli's group proves, it's wildly inaccurate. The poor performance of coded data should really be not too surprising since these codes were developed for billing purposes not epidemiologic surveillance.

The authors performed a systematic review of the literature and found 19 papers for analysis. In each paper coded data was compared to either microbiologic data (C. difficile and MRSA) or manual chart review using standardized case definitions (SSI, VAP, CAUTI, CLABSI). Meta-analysis was performed when enough studies were available. Results are summarized in the table below.

As can be seen in the table, specificity of coded data is generally good to excellent, while sensitivity ranges from bad to horrible. I should mention there is a brand new study looking at CLABSI in the American Journal of Medical Quality, which found a sensitivity of 33% and specificity of 99%.

Perhaps the forthcoming ICD-10 will help, but the fundamental issue of only reviewing physician notes will remain. More sophisticated methods utilizing computerized algorithms for analyzing electronic medical records for case detection will probably be the ultimate solution.

JAMA Infectious Diseases Theme Issue: Deadline April 15, 2014

Just in time for the holidays, Santa has left a gift for ID folks under the tree. I'm not talking about the recent action by FDA to ask the livestock industry to stop using antibiotics for growth promotion, nor am I talking about the FDA's proposed rule to "require manufacturers to provide more substantial data to demonstrate the safety and effectiveness of antibacterial soaps (that contain triclosan or triclocarban)."  While I'm very excited about those developments, I'm pretty sure Santa doesn't work at the FDA.

What I am attempting to highlight is JAMA's ID theme issue planned for October 2014. I offer a few select quotes from the call for papers written by Preeti Malani and Michael Berkwits:

"Ironically, while advances in public health have been driven historically by management of infections, the body of evidence that guides contemporary practice in infectious diseases remains relatively limited."

"Clinical trials rarely can fill a journal issue, and important clinical questions far exceed the number of trials that can be planned, so we invite authors to submit research with other designs and approaches."

"Studies that present new information relevant to optimizing treatment strategies and prevention efforts, and those that enhance the understanding of quality-of-life and economic consequences of infection are also of interest."

Let's hope this theme issue has some new science in the fields of infection prevention, antibacterial resistance and stewardship. Deadline April 15th!

Congratulations, Mike!

Our Health Richmond magazine unveiled their inaugural “Best Bedside Manner” awards this month, and we are not surprised that Mike won first place in the Infectious Diseases category! Mike may or may not wish to comment on whether this recognition will be factored into his compensation plan. Most academic clinician compensation plans reward procedures and inpatient care, and punish ambulatory care providers who spend any sane amount of time with their patients. Let’s hope that whatever healthcare system we eventually settle upon will help restore some balance.

Congrats, Mike!  Every clinician should read (and live by) the quote that accompanies your award announcement.

2013 Studies in Memoriam - A Tribute to Studies Almost Lost

Each year the Academy Awards honors those actors and directors who've died in the prior year. It's one of my favorite tributes. Recently, I found myself with a stack of unread journals about four feet high and one of my routines is to clean my office before the start of each year. Thus, I am catching up on what studies I missed or failed to mention when they were first published. This post is a tribute to those studies that have "almost" died in my journal pile...happy holiday reading...

1) I'm particularly embarrassed that we haven't yet mentioned this review written by Dan. He and Michael Pfaller published a review in the June 1 CID on the promise of rapid microbiological detection of MDRO for infection prevention. Sections cover MRSA, VRE and MDR-GNR. What I really like about this review is that it covers the barriers to successful implementation of rapid detection including the "post-analytic" turn-around time and the current dearth of data supporting the clinical utility for many of these approaches. A must read. (NOTE: Currently the CID website is down, I will update with a direct link to the paper once they are back online)

2) Bevin Cohen from Elaine Larson's group at Columbia published a retrospective cohort study in JGIM investigating gender differences in BSI and SSI risk.  The study included three years (2006-2008) of data from a single center. Odds of these HAI were between 15 to 22% lower in women.

3) John Hollingsworth. Sanjay Saint and colleagues from the University of Michigan published a systematic review and meta-analysis of non-infectious complications of indwelling urethral catheters in Annals this past fall. After identifying and reviewing 37 studies they found that minor complications were quite common. For example, urinary leakage ranged from 10.6% in short-term catheterized patients to 52% in those with long-term catheterization. Serious complications were also quite common. If CAUTI isn't reason enough to remove a urinary catheter, these non-infectious complications should be!

4) And to follow up on the urinary catheter removal theme, there was a meta-analysis published in BMJ that quantified the benefits of antibiotic prophylaxis after urinary catheter removal. When analyzing seven controlled studies (5 from surgical patients), they found antibiotic prophylaxis was associated with an absolute risk reduction of 5.8% for UTI and a risk ratio of 0.45. I suspect there are trade-offs in increased antimicrobial resistance that should be assessed before this is more widely adopted.

Credit: James Taylor at the 2010 Academy Awards - one of my favorite tunes

Does the white coat make the doctor?

There's a new piece in The Atlantic entitled The Psychology of Lululemon (free full text here). I probably would not have read that article but for the fact that I was in Lululemon just a few days ago buying my wife some yoga clothes for Christmas. This turned out to be an interesting read. The premise of the piece is that athletic clothing makes people want to work out--that in some way, clothes have power over the wearer. Of course, I began to think about the implications of the white coat for doctors, particularly because I remembered a survey we did a few years ago where some physicians mentioned that wearing a white coat made them feel more confident. I must admit that at the time I thought that was fairly absurd.

The Atlantic article cites a study from the Journal of Experimental Social Psychology, which I reviewed. Turns out, Eli blogged on this paper last year, so I won't belabor all the details. In a nutshell, investigators at Northwestern University set up a series of experiments in which subjects performed cognitive tasks that measured selective or sustained attention. In one trial some subjects wore white coats and some didn't; interestingly, those who did performed better by a factor of two. In another experiment, all the subjects wore white coats but some were told they were wearing a doctor's coat, while others were told they were wearing a painter's coat. The doctor's coat group scored significantly better. The results led the investigators to coin the term enclothed cognition, which they defined as the systematic influence that clothes have on the wearer's psychological processes.

Rehashing this paper made me stop and wonder whether after being white-coat free for the past five years I should put that dirty old thing back on. It is true that I know some very smart physicians who are never to be seen without their white coats. On the other hand, I also know some white-coated doctors, probably just as many, that I hope to never meet on the other end of a stethoscope. Maybe I'm just too grounded in reality. As much as I wish that if I ensconced myself in Under Armour my athletic abilities would surge, there's not enough magical thinking on earth to tear me from the bitter reality that my skinny, scrawny body would not perform any differently.

While I'll have to bow to science and come to grips with the concept of enclothed cognition, I still believe that keeping patients from contact with contaminated coat sleeves trumps whatever small intellectual edge the white coat might provide. As the psychologists have shown, it's all in your head. So here's my recommendation: as you enter your next patient's room, bare below the elbows in your freshly laundered scrubs, stop for a split second and imagine yourself sporting a shiny white coat in all of its radiant splendor with a Superman logo blazing above the chest pocket. Then strut confidently into that room, and bedazzle the patient with your diagnostic brilliance.  

Great news for patients with C. difficile

At this point in time, I've performed about 50 fecal transplants. I find these procedures to be both a blessing and a curse. They are amazingly effective for patients with recurrent C. difficile. Many of my patients have had chronic diarrhea for months, and are unable to leave their homes. So imagine how incredible it is for them to be cured within 24 hours of a fecal transplant. I have heard over and over, "you have given me back my life." And I have to admit it's a blessing for me, too. Rarely in medicine do we see such rapid and dramatic cures. What's not to like about this? How could it be a curse?

Well, as we have blogged before, the logistics of fecal transplantation are difficult and there are a number of barriers. While most patients don't have difficulty finding a donor (usually a family member), some elderly patients don't have a donor. Cost is also a barrier. Donor testing is not covered by insurance, so the out-of-pocket cost is up to $1500. For poor patients, this is quite a problem, and I've had patients whose family members all chipped in to pay for donor testing. Then the donor has to "perform" at a specified date and time (and sometimes they can't).

The transplant I did yesterday was fairly typical. I went to the clinic to pick up the donor specimen and ran it to the lab (10-15 minute round trip), where our laboratory technician began the dirty work of homogenizing the stool sample in a blender and filtering it. While she was doing that, I ran back to the clinic, got the informed consent, inserted the NG tube and sent the patient to X-ray for confirmation of tube placement. The queue in x-ray can be up to 45 minutes. While the patient was in X-ray, I ran back to the lab, picked up the prepared specimen and returned to clinic. When the patient returned, I injected the NG tube with the fecal slurry, flushed the tube with some water, then removed the tube. On most days, all of this takes 2-3 hours of my time. If insurance pays us, we collect less than $75. During the same time period, my colleagues will generate charges that are roughly 6-9 fold higher than mine. Since most of us now work in an RVU-based compensation model, it should be apparent why so few physicians do this work. But I can't not do it, even though it reduces my salary. I feel morally compelled to help these patients who are so desperate, particularly when I know that the odds are very high that I can cure them with a simple procedure.

Yesterday I stumbled on OpenBiome's website and as I explored it I was nearly euphoric. OpenBiome is a non-profit started by four students (a molecular biology PhD candidate, an MBA candidate, an MPA candidate, and an MD/MBA candidate) at Harvard, MIT and Princeton. The company provides processed, frozen human stool from donors that have been carefully selected and screened for multiple infectious diseases at least twice, at a cost that's 1/6 the price of me testing one donor, and 5 to 14-fold cheaper than the drugs that these patients have taken without success. And OpenBiome's goal is to reduce the price even more as they scale up their operation. I had a long conversation today with James Burgess from OpenBiome. He knew so much about C. diff that I assumed he was the medical student, but he's actually the MBA student. He was excited to tell me about their work and I was incredibly impressed. They have covered all the bases, including banking serum from donors for future testing should a patient develop an unusual infection.

So Kudos to OpenBiome! Many patients will benefit from their ingenuity and generosity. And they'll make my job a whole lot easier.

Resistance versus Virulence

The conventional wisdom is that bacteria pay a “fitness cost” as they accumulate antibiotic resistances, a phenomenon I discussed in a short post last year. More resistant, but less fit, and (one hopes) less virulent. Thus some of the most problematic multi-drug resistant organisms (MDROs), such as Acinetobacter, cause disease almost exclusively in the most vulnerable patients—those bugs simply aren’t virulent enough to wreak their havoc in the healthy. When an MDRO does emerge as a major community scourge, as was the case with community-associated MRSA, it’s big news.

So I was surprised (not pleasantly) to read this report in PNAS about Pseudomonas aeruginosa strains that refused to adhere to convention. Using a mouse model and well-characterized P. aeruginosa mutants, the investigators found that strains with mutations in a gene encoding a particular outer membrane protein (one that provides an entry channel for carbapenem antibiotics) were more virulent—more likely to disseminate from the mouse GI tract, and more resistant to in vitro killing by acidic conditions or human serum. Now mice are not men, and a murine gut colonization model isn’t necessarily predictive of an organism’s ability to cause infection at various human body sites. Still, it is nerve-wracking to know that our carbapenem use might produce P. aeruginosa strains that are not only more resistant, but also more virulent! As the title of the accompanying editorial points out, it is indeed a “worst case scenario”.

Scanning EM of P. aeruginosa from the Public Health Image Library

A Urinary Catheter's Perspective

Martin Kiernan, Infection Prevention Consultant at Southport and Ormskirk NHS Trust in the North-West of England, penned the Catheter's Lament while on the train to the IPS conference this year. It was the last slide of his EM Cottrell Lecture, "The Life and Times of the Urinary Catheter." Graphics courtesy of Clinidirect. Thanks to both for sharing.

A specialty in decline?

It was “match day” today for the internal medicine subspecialties. For some fields, there are far more applicants than training positions. Thus hundreds of would-be gastroenterologists and cardiologists find themselves out in the cold, unable to pursue their chosen profession. Not so for infectious diseases (ID). This year marks a new record for unfilled ID programs (54), with many training programs unable to fill a single training spot in the match. Given current trends, we are approaching a situation in which half of all programs will have unfilled positions. As funds for graduate medical education become increasingly scarce, some of these programs will likely reduce the number of training positions they offer, or shut down altogether. 

There are several explanations for this trend, including reimbursement of ID specialists (train longer to make less!), the educational debt burden of trainees, the rise of the hospitalist, and reductions in research funding for academic careers. I have no easy answers, but it is urgent that we address this slow motion train wreck. Multiple drug resistant bacteria already far outnumber the contingent of ID doctors, and that situation is bound to get worse over the next several decades. Some things to work on: (1) perform studies to demonstrate the value provided by the ID specialist, (2) advocate for increased funding for ID research and training, and (3) provide role models who demonstrate that ID is an incredibly interesting and rewarding career!

Word of the day: crapsule

There's a great article in The Atlantic on fecal transplants for C. difficile infection (free full text here). What I like about this piece is that it describes the very real barriers to fecal transplantation without any sugar coating. It also highlights the work of Dr. Bruce Hirsch, an infectious disease doctor who crafts capsules with fecal bacteria (or "crapsules" as he calls them) so that patients can be transplanted without an NG tube or colonoscopy.

Photo:  Salon.com

The beginning of the end for...CHG??

Chlorhexidine. We love it, we just can't get enough of it, we are up to our neck in it and we cheer for it. Basically it's the greatest. But some of us have been concerned that the widespread use of CHG would lead to resistance, particularly in Acinetobacter.

There is a new report in PNAS by investigators in Australia and the UK that looked at gene expression in A. baumannii after chlorhexidine exposure. The most highly up-regulated genes were those encoding the RND efflux system AdeAB. Importantly, the investigators also identified a gene encoding a previously uncharacterized membrane protein, AceI, which they determined to be an active CHG efflux protein capable of transporting CHG out of the cell. This novel AceI was said to be a member of the PCE family of efflux systems.

And to give you a sense of the ubiquity and potential importance of these systems in Gram-negative bacteria, I offer this quote from the authors:

"The primary features of the A. baumannii chlorhexidine resistance response, i.e., up-regulation of genes encoding RND and PCE family efflux systems, are conserved in other γ-proteobacteria, as well as β-proteobacteria. Given the phylogenetic distance of these organisms, this similarity of regulatory responses to a compound that has only been synthesized since the early 20th century is intriguing. RND efflux systems are well recognized for their broad protective functions in Gram-negative bacteria and it is not unusual for these systems to constitute part of a general stress response and to mediate resistance to foreign compounds, particularly amphipathic antimicrobials such as chlorhexidine. However, the involvement of the PCE family proteins in seemingly specific resistance to chlorhexidine is unexpected. It is likely that the physiological function(s) of this transporter family were originally unrelated to chlorhexidine resistance and that these proteins provide a fortuitous intrinsic resistance capacity."

h/t Ayush Kumar and Dan Ricciuto

image source: wikipedia

Six dangerous words

There's an interesting essay in JAMA this week entitled EBM's Six Dangerous Words. In it, Scott Braithwaite argues that physicians should banish the phrase "there is no evidence to suggest that..." He gives as an example: there is no evidence to suggest that looking both ways before crossing a street compared to not looking both ways reduces pedestrian fatalities. While that's technically true, as he puts it, such statements presume "a definition of evidence that requires formal hypothesis testing in an adequately powered study." It makes objective certainty the be-all and end-all, and "is ambiguous while seeming precise." I have heard hospital epidemiologists state that there is no evidence to suggest that white coats can transmit infections in the healthcare setting. Ok, but sometimes the common sense of the average Joe trumps the best the medical literature has to offer. Or so it should...