More good news about MRSA. This time from VA.

It's not often that good news about hospital-acquired infections (HAI) is reported in the media. When was the last time you read an article congratulating a hospital for having lower CLABSI rates or good hand hygiene compliance? It's even rarer to hear good news about VA Medical Centers. While the quality of care in VA often meets or exceeds that in the private sector, it's rarely reported, since high quality runs contrary to established memes.

That's what's unique about today's 'Opinionator' article in the NYTimes. It reports greater improvement in MRSA infections in VA vs non-VA hospitals. To those of us that study HAI and resistant bacteria, this isn't that surprising. Integrated, public (national) health care systems, like VA, have built in incentives to prevent infections since they see the direct benefits of reduced costs and better outcomes - incentives that aren't well-aligned in other hospitals. However, to most folks it is probably surprising that VA was an early adopter of a bundled approach to MRSA prevention and has set the bar for the rest of the country.

Dan and I are both quoted in the article, so I encourage you to read it. However, I'd also like to highlight one section:

"The V.A.’s achievement is even more remarkable because its patients are older and sicker than patients in other hospitals. (Most patients are Vietnam-era vets. None are healthy young women giving birth, a large patient group in most hospitals.) They are twice as likely to come to the hospital already testing positive for MRSA. The greater the percentage of people who have the bacteria, the harder it is to control its spread. Because their immune systems are weaker, V.A. patients are also more likely to go from testing positive to full infection."

The fact that VA patients are older, sicker and often poorer than other hospitalized patients is frequently missed in the wider discussion about quality measures. When you have all the cards stacked against you and you still deliver high-quality and safe care, it should be recognized. Nice when it is.

Ebola - Some Hope for Control in West Africa

Ebola, as we all know, is out of control. As an example, every time I turn on the TV there is Dan or Mike or Dan staring back at me. Eventually, we will calm down in the US and begin to focus our attention on the critical outbreak in West Africa. My prediction is that this will happen sometime soon after November 4th (Election Tuesday). In the meantime, there is some possibly, maybe, hopefully good news out of West Africa in today's NYT. As of a few days ago, fewer than half of the 649 available treatment beds in Liberia were occupied. Of course this could be good or bad, but I'm holding out for good.

There was also some potentially good news in a report published in the Annals yesterday. Dan Yamin et al. analyzed a stochastic model of Ebola transmission populated with parameters from a 2000-2001 Uganda outbreak and the current outbreak in Montserrado County Liberia. The authors used the model to determine the number of secondary cases infected by survivors or non-survivors and also evaluated the effect of isolating/hospitalizing patients. I have included the key figures from the paper below. In Figure 1a, they estimate the Ro stratified by whether the index case was a survivor or non-survivor. For the whole cohort, the Ro was 1.73. However, the difference between non-survivors and survivors is striking. It appears that non-survivors infect four times as many people as survivors (2.36 vs 0.66). This may explain why the two Dallas nurses were infected after being exposed to a non-survivor while no secondary cases have yet occurred in other US hospitals, where everyone else (so far) survived.

Figure 1a

In Figure 1c, the authors provide an estimate of the average number of secondary cases per day of symptomatic disease. You can see that there is very little transmission in the community at day 1 and it remains very low for survivors but jumps up after day 2 for non-survivors. This implies that waiting for symptom development is a scientifically valid strategy for preventing community transmission of Ebola even in Africa. (We expect these numbers to be far lower in the US where our communities are less crowded and we are fortunate to have toilets, indoor plumbing and clean water.)

Figure 1c

Finally, in Figure 2 the authors evaluated at what time point non-survivors (very sick individuals) must be actively isolated to prevent community transmission. They estimate that if 75% of the non-surviving cases are detected and isolated by day 4 this results in a 74% chance of disease elimination and if 100% are detected and isolated by day 4 then there is a 94% chance of disease elimination. Currently, the authors report that the average time from disease onset to hospitalization in Liberia is 5 days, so there is some room for improvement. However, I suspect that the current expanded efforts could achieve 4 days. When I put the results of this Annals paper together with the NY Times report of empty beds, it suggests that there is available capacity to hospitalize and isolate patients within 4 days of symptom onset and it might even suggest that current efforts are already working. I'm certainly hoping this is the case.

Oh, and if isolating patients 4 days after symptom onset works in West Africa, it means WE DON'T NEED TO QUARANTINE ASYMPTOMATIC FOLKS IN THE US. So please stop it...and sorry for shouting.

Enterovirus 68 in 38 States

Yesterday, CDC released updated statistics that describe the emergence of EV-D68 in the US. Last month the virus appeared in Missouri and Illinois but quickly spread with 226 confirmed cases now in 38 states. Clearly these numbers underestimate the extent of EV-D68 illness since most hospitals are unable to test for this virus and once it's confirmed in a region, additional testing provides few benefits.

The NY Times reported that the University of Chicago Medicine Comer Children’s Hospital had to go on diversion three times in the last month because their emergency department was filled with children suffering from acute respiratory illnesses. Prior to this outbreak, they hadn't diverted ambulances in 10 years. It is possible that other viruses are contributing to the problem; however, CDC reports that of the specimens sent to their lab about half were EV-D68 positive and a third were positive for other enterovirus or rhinovirus strains.

The NYT article also mentioned that Children’s Hospital Colorado saw ~3,600 children in the past month with approximately 10% requiring hospitalization. Christine Nyquest, the hospital epidemiologist quoted in the article, stated that her hospital was facing a bed crunch and having difficulty maintain adequate supplies of albuterol.

Meager and unsatisfactory

It’s nice to see antimicrobial resistance featured in a Sunday NY Times editorial—nothing that we haven’t already covered in Eli’s recent post on the WHO report, but worth reading nonetheless. 

If you believe that “you can’t improve what you can’t measure”*, the most disheartening sentence in this editorial about the WHO report is “…few countries track and monitor antibiotic resistance comprehensively, and there is no standard methodology for doing so."

*This saying is a paraphrase of Lord Kelvin, who also said:

“When you can measure what you are speaking about, and express it in numbers, you know something about it; but when you cannot express it in numbers, your knowledge is of a meagre and unsatisfactory kind.” 

“Meager and unsatisfactory” is a great description of the status of our current response to the antimicrobial resistance threat.

Presenteeism makes the Sunday NY Times

As regular readers know, “presenteeism” (coming to work while sick and potentially infectious) is a frequent topic on this blog. It’s nice to see the issue getting wider attention, this weekend in the pages of the New York Times. Go ahead and read Danielle Ofri’s excellent piece on the topic, from which I’ve pasted a couple quotes below:

“This, of course, is ridiculous behavior on the part of medical professionals who would never recommend such nonsense to their patients. Medical workers with respiratory infections are contagious. Caregivers with gastrointestinal infections — as I had — can easily infect their patients. ….  

What we can do, however, is examine the existential qualms that doctors have about illness. From the beginning of medical school it is important to advance the idea that illness is a part of all of us — doctors and patients alike; that there is very little that separates us from our patients, other than the circumstance of the moment; and, for goodness’ sake, that we need to call in sick when we are sick.”

Antibiotic Discovery: Focusing on supply while ignoring demand is doomed to fail

There is an article in today's New York Times (above the fold on page one - see image) that brings the problem of antimicrobial resistance and antibacterial discovery to the public's attention. It's a very important issue and many of the points raised in the article are spot on. Just some things for you to think about when you read the article:

1) Health and Human Services is giving between $40 and $200 million to GlaxoSmithKline over the next 5 years for drug discovery. This amount approximates what NIH spends on all antimicrobial resistance research for ESCKAPE pathogens ($50 million annually).  It's surprising that this amount couldn't be targeted to NIH or CDC funding instead (or ever).

2) Frustratingly, there was not one mention of antibacterial stewardship or infection prevention. Back when I was studying economics under this guy at University of Michigan, I learned about price determination. In principle, the price for a good will tend to settle where demand equals supply. I think of antimicrobial resistance the same way - demand is the need for broad-spectrum antibiotics based on resistance levels in the community and supply is the availability of effective antibiotics to treat resistant infections. If we focus on the supply side by funding pharmaceutical companies, we may end up with more effective antibiotics, but the set point equilibrium with high levels of resistance will remain if we continue to ignore the demand side.  To fix the demand side we need equal investment in stewardship and infection prevention research and implementation. Give $200 million to prevention research and we might actually find ways to scientifically achieve hand hygiene compliance over 50% without just yelling at health care workers! Imagine that...pause...

What did grandma tell me when I was little? - "an ounce of prevention is worth a pound of cure." I think she was spot on and it's is probably why I became a hospital epidemiologist. Thanks grandma.

Rory

In this morning's New York Times, Maureen Dowd's op-ed piece is about Rory Staunton, the 12-year old boy who recently died from an invasive group A strep infection. Rory's story was chronicled in the New York Times earlier this week in a lengthy piece by Jim Dwyer. I have thought a lot about this case over the past several days. It's a tragedy for all involved.

Ironically, over the past few weeks I've been reading the new edition of Bob Wachter's text, Understanding Patient Safety. I plan to review the book on this blog in the near future. The issues at play in Rory's case are all described in Wachter's book. There were both systems issues (e.g., laboratory data that were not acted upon because they arrived after the patient had been discharged from the emergency department) and medical decision-making issues. When the case is laid out in the well-written piece by Mr. Dwyer, it seems fairly obvious that this boy was critically ill and should never have been discharged. Yet what we can't see is what else was happening at that time that may have influenced the physicians' decision making. Many potential explanations are put forward in the 1,500 comments on the New York Times online edition.

In my conversations with Mr. Dwyer as he was writing the article, I questioned him about whether the child had a necrotizing soft tissue infection. Though no diagnosis was made (at least antemortem from what we know), this appears to be a classic story for such. Two hallmarks of necrotizing soft tissue infection were present--pain (typically in a limb) out of proportion to what you would expect from visual inspection of the area and toxicity out of proportion to what you would expect. Often these cases occur after relatively minor trauma, so minor that patients often don't think to initially tell physicians about it. In Rory's case, I suspect that the traumatic injury to his leg occurred when he dived for a ball during gym class.

In my experience, the diagnosis of necrotizing fasciitis or necrotizing myositis is not considered early in the presentation as the findings on the skin over the deeper infection are initially subtle. Often the infectious diseases physician is the first to consider the diagnosis, but the consultation may occur after critical time has passed. Importantly, severe pain in a limb with Group A strep growing in blood cultures is a necrotizing soft tissue infection until proven otherwise. However, the disease needs to be considered before the blood cultures turn positive (which often takes 12 hours or so). The natural tendency is to obtain imaging of the limb to look for the cause of pain. However, plain x-rays do not provide useful information and CT scans typically do not help either. Often, clinicians will falsely conclude that necrotizing infection is not present because imaging shows no gas in the soft tissues; however, group A strep does not produce gas. MRI can be useful but at most hospitals MRIs are difficult to obtain promptly as schedules are tight, and additional time can be lost. Diagnosis can be made quickly by having the surgeon make an incision over the suspected area, visually inspect the muscle and probe the fascia. If a necrotizing infection is found, debridement of devitalized tissue is then performed. The critical issue is that the diagnosis of group A strep necrotizing infection is often delayed and even when suspected by an astute clinician, other physicians involved in the patient's care may not act quickly to establish the diagnosis. Thus, the infectious diseases consultant may spin his wheels trying to convince other physicians of the suspected diagnosis.

My hope is that Rory's case will raise awareness of invasive group A strep infections for clinicians, and prompt hospitals to examine the systems issues at play in this case. His family has already established a website focused on raising awareness. 

Rory's story is a reminder that medicine remains a human endeavor fraught with peril and that even well-trained physicians practicing in sophisticated settings err. When I read a story like this, I get a sick feeling in the pit of my stomach as I think but for the grace of God that could have been me making similar clinical decisions that led to a terrible outcome. I continue to find the practice of medicine a humbling experience as I am reminded often of how rapidly the corpus of medical knowledge is expanding.

The two pieces about Rory in the New York Times paint a picture of a really good kid who wanted to make a difference in this world. And I suspect that in the sharing of the story of his final days, he has.


Photo: New York Times

When medical-decision making goes awry

There is a very sad case report in today's New York Times that describes a missed case of S. pyogenes sepsis in a 12-year-old boy.  The initial diagnosis of viral gastroenteritis resulted in an ER discharge that delayed therapy.  Our very own Mike Edmond discusses the case in the article.

We've all lost sleep at night since we first started medical school worrying about cases like this.  It's pretty easy to fall into the false belief that we can avoid these misses in the care of our own patients, but sadly we're all susceptible to the frailties of the human mind and cognitive biases.

Some of the biases that I think impacted this sad case were highlighted in a 2010 American Medical News article by Kevin O'Reilly and include:

• Anchoring bias – locking on to a diagnosis too early and failing to adjust to new information. 
• Availability bias – thinking that a similar recent presentation is happening in the present situation. 
• Confirmation bias – looking for evidence to support a pre-conceived opinion, rather than looking for information to prove oneself wrong. 
• Diagnosis momentum – accepting a previous diagnosis without sufficient skepticism. 
• Overconfidence bias – Over-reliance on one’s own ability, intuition, and judgment. 
• Premature closure – similar to “confirmation bias” but more “jumping to a conclusion”

Until diagnostic systems can be designed that can help prevent these biases from intruding on our decision making, sadly these horrible cases might not be 100% preventable.

Epidemiological surveillance testing is a waste

Only last month, we posted on the Washington state pertussis outbreak. Back then, there were 640 reported cases through March.  A month later there are 1284 total cases, up from 128 the prior year.  To me, these seem like important data. For one, we've used them to sound the alarm over low vaccination rates.  Now an article in today's NY Times highlights the impact that state budget woes have had on the public health infrastructure and how this has blunted the epidemic response.

Skagit County's (pop: 117,000) top medical officer, ER doc Dr. Howard Leibrand, has some choice words for pertussis testing, which I've pasted below:

If the signs are there, he said — especially a persistent, deep cough and indication of contact with a confirmed victim — doctors should simply treat patients with antibiotics. The pertussis test can cost up to $400 and delay treatment by days. About 14.6 percent of Skagit County residents have no health insurance, according to a state study conducted last year, up from 11.6 percent in 2008. 

“There has been half a million dollars spent on testing in this county,” Dr. Leibrand said late last week. “Do you know how much vaccination you can buy for half a million dollars?” And testing, he added, benefits only the epidemiologists, not the patients. “It’s an outrageous way to spend your health care dollar.” 

Since antibiotic overuse has no cost or downsides from a public health perspective and we don't need to understand the scope of the epidemic, this is probably cool.

Image source: www.healthheritageresearch.com

Manuscript Provenance: Why NEJM has a high retraction rate (and it's not a reason mentioned in the NYT)

A recent high-profile story in the NYT by Carl Zimmer discussed a surge in article retractions since 2000. Over the period 2000 to 2009, retractions have risen by 3300%. (see calcs below) The Time's article draws much of its data and discussion from a pair of editorials published by Ferric Fang and Arturo Casadevall covering "structural reforms" and "methodological and cultural reforms" and a recent news feature in Nature. I highly recommend the two calls for reform from Fang and Casadevall, which cover topics ranging from increased administrative burden to problems with grant review. However, it is hard to make a link from any of these problems and scientific error or misconduct without further research.

For example, much of the discussion falls into the category of "survival of the fittest" with scientists doing everything possible to publish in high-profile journals (e.g. NEJM), which then is supposed to lead to increased grant funding and wealth.  I'm not denying that this could be a factor in scientific fraud, but it's hard to imagine this would increase errors, directly. If you look at the NYT graphic (above), fraud is associated with a minority of all retractions. To provide evidence that a scientists desire for fame is driving the retraction epidemic, Fang and Casadevall, published another editorial that included an analysis linking impact factor of the journal to a retraction index. They found that the higher the impact factor, the higher rate of retraction with NEJM at the top.

Reasons given for the association include higher risk-taking by authors in papers submitted to high-ranking journals and that publications in high-impact journals may just be subject to greater scrutiny (e.g. via social media). These reasons are appealing, although I'm not sure there's a testable hypothesis among them. One testable "systemic aspect of the scientific publication process" that is likely to be associated with both journal rank and retraction (and more likely to be causal) is a manuscript's provenance.

Manuscript Provenance
In the art world, a painting's provenance refers to the chronology of ownership of a specific painting or work.  When I speak of a manuscript's provenance, I mean where it's been submitted and received peer review prior to publication.  As anyone who has submitted a manuscript knows, you almost always submit the paper to a higher-impact journal first and then if not reviewed or accepted, you aim a bit lower.  In fact, there is only one paper we've submitted out of >100, that's gone initially to a lower-ranked journal and then when rejected, was submitted and accepted by a higher-ranked journal.

Thus, manuscripts submitted and accepted at higher-ranked journals are more likely to have been reviewed only once, or received one round of peer review. Yes, I know that some papers go to JAMA then NEJM and some papers are submitted directly to a specialty journal and are reviewed once, but in general, papers published in higher-ranked journals have been through fewer rounds of peer review.  Unfortunately, these data are not easily available, but it's likely this hypothesis can be tested. Nevertheless, I think quantity of peer review is an important predictor of quality of the final product.  It is unlikely that more peer review could detect outright fraud, but most retractions aren't fraud related.

So before we blame the entire system for a few bad apples, there need to be more epidemiological studies as to why this is occurring.  My first suggestion is that we should consider manuscript provenance as a factor and my second suggestion is that journals should pay for peer review, so that it becomes a valued exercise.  Peer review service should also be considered for promotion. Sure the system could be improved in many ways, but it's a stretch from there to finding a causal pathway between a journal's impact factor and a higher retraction index. Oh, and this is all probably because of twitter anyway.


***Retraction Rate Calculation: Using rates of 3/year in 2000 to 180/year in 2009 from the NYT article and given that there's been a 64% increase in PubMed articles  (529,000 in 2000 to 866,000 articles in 2010), this represents an increase from 0.0006% to 0.02%, or a 3300% increase.

Control groups are for losers

That’s what I learned from today’s New York Times editorial. In their review of the two NEJM studies we covered last week (here and here), they describe the VA study as “broader” (true, if by broader they mean larger) and “possibly more rigorous” (untrue). They also point out that “if other hospitals could replicate the effort, thousands of patients might be saved from needless infections”. The editorial board at the NY Times should know that hospitals across the country are already saving thousands as MRSA HAI rates drop nationwide! And many of these hospitals are saving lives without also stimulating the economy by doing universal MRSA screening. A bundle with multiple interventions, one of which is unproven and hugely resource intensive, doesn’t seem in keeping with the spirit of health care reform. And sadly, determining the proper role of the most expensive element in the VA's MRSA bundle requires studies that use something we epidermatologists like to call a “control group”.

the New York Times is dead to me

Dan, Mike and I have frequently posted on content from the NY Times. As most of you have heard, on Monday the NY Times began charging for digital content.  This is the so called pay wall or pay fence or pay sponge. I have no problem paying for digital content as I subscribe to the Economist, National Geographic, etc on my iPad with specific apps or through Zinio, which is a great app if you haven't tried it. What troubles me with the Times current plan is that they are charging me based on what device I use to read their content.  I mainly read the NY Times (and everything else) on my iPad and phone.  With other digital subscriptions this doesn't matter since I pay a single amount and can access on any device. For example, the Economist charges $110 for a year subscription no matter how I read their content. The NY Times, however, has decided that they will charge $15/4 weeks ($195/year) to read on a phone and an additional $20/month ($260/year) to read the same content on an iPad, for a total of $455/year.  Crazy.

I know there are work arounds like linking off Facebook or through google searchs, but do I really want to do that?  I could also enter my username and password each time and just read on the iPad browser, but that is not the point.  I know I could subscribe to the Sunday Times for $8/week ($416/year) and save $39, but I don't really want to kill trees and waste fuel and this option isn't available in all places.  It is almost like they don't realize there is a digital age upon us.  Netflix doesn't care if I stream on a TV, laptop, or phone and why should they? Do they have extra reporters giving me inside information that only goes to my iPad? No!  There is almost no additional cost (marginal cost) for them to upload the same content to my iPad or phone, so it makes no sense for me to spend $260/year for something that costs them nothing.  They need to join the 21st century and not race back to the past. I thought the Times was called the Gray Lady since it had few pictures, but perhaps there is another reason. So, until they offer one price for digital access, the Times is dead to me.  I won't read (all bookmarks and apps removed) and I won't review, link or comment on NY Times generated content.

EOR

Economist online subscription page (so you can see what the world could look like)

WBUR's On Point has a great discussion on this subject that you can listen to.

Cholera in New York City

I know it isn't Friday, but strictly speaking this is a fecal-oral post and not just a feces post.  Three cases of cholera were recently confirmed in NYC residents returning from a Dominican Republic wedding.  NYC typically sees 1 case/year of confirmed cholera.  All three people fully recovered without hospitalization, so no hospital infection prevention issues in this incident.  Even if a patient was admitted, transmission in hospital would be extremely unlikely.  Even then, something to be aware of.

Link:  NY Times story 2/5/2011

Scientists create new bacteria out of nothing

Just reported in the journal Science, Craig Venter's group has created Mycoplasma mycoides out of nothing. Now if they could just create a new antibiotic!

http://www.nytimes.com/2010/05/21/science/21cell.html