Woo woo! Senate passes FDA Food Safety Modernization Act

Thanks Senator Harkin

Not too much to say, that I haven't said before. Today the Senate passed the FSMA bill 73-25-2. This bill was actually introduced in March 2009 and would cover 80% of the food supply excluding meats. This seems like a nice example of bipartisanship. The NY Times mentioned that Republican and Democratic Senate staffers met for the first time in ages and 'broke bread' with Starbursts and jelly beans. Let's hope this gets out of committee in time or is simply passed by the House as is. Would be sad to see this die when the clock runs out.

Final quote: “This legislation means that parents who tell their kids to eat their spinach can be assured that it won’t make them sick,” - Senator Tom Harkin (D-Iowa)  Of course, anyone who needs to figure out how to get their kids to EAT their spinach, should check out my friends Laura and Jennifer's book from the American Academy of Pediatrics: Food Fights: Winning the Nutritional Challenges of Parenthood Armed with Insight, Humor, and a Bottle of Ketchup

NY Times article 11/30/2010

Don't pull that trigger!

The headline on the front page of the New York Times this week read "Study Finds No Progress in Safety at Hospitals." This article (graphic shown) reported on a paper in this week's New England Journal of Medicine (free text here). In this study, 240 charts from each of 10 hospitals in North Carolina were reviewed using the Institute for Healthcare Improvement's (IHI) Global Trigger Tool. The admissions reviewed spanned the years 2002 to 2007.

Now I didn't know much about the Trigger Tool and the methods section of the paper doesn't give much description, so I looked up the guide, which you can review here. The triggers are 53 different indicators that when observed in the medical record should prompt further review to assess for an adverse event. For example, administration of benadryl is a trigger to look for a drug allergy, which according to IHI is an adverse event. Adverse events are further classified by severity and whether they were preventable. Per the IHI guide, no more than 20 minutes can be spent on the review of any chart (that rule was also observed for the published study).

Per the IHI methodology, healthcare-associated infections are both a trigger and an adverse event. Here is what the guide states (p.17):

Any infection occurring after admission to the hospital is likely an adverse event, especially those related to procedures or devices. Infections that cause admission to the hospital should be reviewed to determine whether they are related to medical care (e.g., prior procedure, urinary catheter at home or in long-term care) versus naturally occurring disease (e.g., community-acquired pneumonia).

Note that HAIs are never defined. Unlike the CDC's National Healthcare Safety Network (NHSN), which defines infections using multiple data points, IHI methodology doesn't guide the reviewer as to case ascertainment. I did a PubMed search this morning and found no studies where the Trigger Tool was compared to NHSN methodology to assess its validity.

So here are some concerns I have about this paper and the Trigger Tool:

• By design the Trigger Tool is not true surveillance. There is no attempt to detect all instances of harm. Imagine looking at the medical record of a patient who stayed in the hospital for 8 months with a 20-minute time limit. While I can understand how the Trigger Tool might uncover problems in any given hospital using a case-based approach for quality improvement, to look for trends over time using these data doesn't make any sense since there is no attempt to capture all the cases of harm. Of what value is trending incomplete data? I think this harkens back to the philosophical differences between quality improvement and healthcare epidemiology that I've talked about before. 
• I have serious concerns regarding the validity of this approach for HAIs. We know how problematic surveillance can be even when using well-delineated case definitions and how poorly administrative claims data perform for HAIs. The IHI approach seems much more analogous to the administrative data approach.
• In the New England Journal paper the secular trends were shown only for all harms and preventable harms, but not for any of the component harms, such as HAIs. It would be interesting to see the trended data for HAIs. Recall that AHRQ, using administrative claims data, recently published a paper claiming that HAIs are increasing in the US, while CDC, using much more rigorous surveillance methodology, published the opposite conclusion.
• Generalizability seems to be problematic. In this paper 2,400 hospital records were reviewed from 10 hospitals in a single state. Over the same time period, there were approximately 220 million hospital admissions in the US. That means that about 1 in 100,000 hospital admissions were reviewed (and only partially given the 20-minute rule). While the published paper never attempts to generalize the study findings to the universe of US hospitals, the media certainly did, and the lead author of the study states in the New York Times, “It is unlikely that other regions of the country have fared better.”
• Some of the instances of "harm" are not preventable and I'm not sure how they are related to quality of care. For example, consider the case of a patient with no known drug allergy who is treated with an antibiotic and develops a rash. This would be classified as a harm, and it is indeed a harm to the patient, but it's not predictable and not preventable. How does it help us to trend such data? And how would we attempt to reduce this harm? It is preventable harm that needs our attention. 
• With regards to HAIs, even if these data were valid, I don't believe these data reflect the current state of affairs in US hospitals given that much improvement in infection rates has occurred since 2007.

So here we have another paper that beats us up some more. If truth be told, I bet that the quality of care in US hospitals is significantly better today than it was in 2002. It sure would be nice to see that in print, but it probably wouldn't hit the front page. 

P.S. It's amazing that IHI claimed to have saved 123,000 lives in the US due to its safety program for US hospitals, but now claims that during the same time frame there was little evidence of improvement in patient safety. Something doesn't compute......  

PEP, PrEP, or even PeEP?

I finally got around to reading the paper in the New England Journal on the use of daily antiretroviral therapy for the prevention of HIV infection (full text here). In hospital epidemiology we're very familiar with post-exposure prophylaxis (PEP) for healthcare workers who sustain percutaneous exposures or blood/body fluid exposures to mucous membranes. This paper evaluated pre-exposure prophylaxis (PrEP) for men who have sex with men by having the study subjects take a daily dose of truvada. New HIV infections were compared in the treatment group to men who were assigned to take a placebo daily. There were roughly 1200 men in each study arm. On average the men were in their late 20s, had more than 1 sex partner weekly, about 60% reported unprotected anal intercourse, and they were followed for roughly 1 year. There were 36 new HIV infections in the Truvada group (2.9%) and 64 new infections in the placebo group (5.3%). This represents a 44% relative risk reduction. Sounds pretty good, but that translates to only a 2.4% absolute risk reduction (the infection rate in the treated group subtracted from the infection rate in the placebo group). When the subset of men with detectable drugs levels (i.e., those who were compliant with Truvada) were compared to those without detectable drug levels, the relative risk reduction was 92%. "That's huge," exclaimed Dr. Anthony Fauci, the head of the National Institutes of Allergy and Infectious Diseases, in the New York Times.

So here we have an intervention that appears to be efficacious but not effective (that is, it works when you take the drug, but in the real world many people just won't take it--we've talked about this before). By my calculations, compliance appeared to be about 38% in the study. However, I think we can be sure that compliance would have been even less in the real world if the study subjects had to pay for the Truvada at the retail price of $13,000 yearly. We're also not told whether those who took the drug faithfully may have also been highly compliant with condom use, which may make the drug appear to be more effective than it actually is. So, in the end, I don't think that the impact of this study will be huge. In fact, I doubt it will have much impact at all. The real issue, it seems to me, is helping people to reduce risk the old fashioned way (fewer sexual partners and consistent use of condoms), until the day finally arrives when we have an effective vaccine for HIV.

Switching gears, as a hospital epidemiologist, I wondered if there is a role for PrEP in the hospital. Let's consider the case of a an untreated HIV infected patient with a high viral load who needs cardiac or orthopedic surgery soon. Should the operative team be given PrEP or perhaps peri-exposure prophylaxis (PeEP), with dosing the day before, the day of the procedure, and the day after? If I were the surgeon, I would be interested in that.

Why we can't work at work

In my previous post, I mentioned what I was going to read during my quiet time this weekend.  We all have to work like this now, since it has become increasingly difficult for us to get work done at work. Our homes are now our offices. What we need is no-talk Thursdays or something like that. This Jason Fried TED video explains:

link for non-flash devices (iPhone etc)

Thanksgiving Reading List

I just ripped out a few articles to read over the upcoming holiday.  I may have more things to say on these subjects in the future; however, I didn't want you to lack good reading material for the long weekend.

1) Hospital-acquired C. difficile is associated with 3-fold risk of death which diminishes as baseline severity increases. (source: Oake N et al, Archive Intern Med. Nov 8, 2010)

2) The 7th Edition Mandell, Douglas and Bennet's Principles and Practive of Infectious Diseases is bigger and better than ever- Book Review by Preeti Malani. (source: Malani P JAMA Nov 10, 2010) the book is only 4328 pages, so you can have until Dec 31 to read this one. (Note: I did not specify a specific year)

3) Intentional infection with STDs (GC, chlamydia and syphilis) in vulnerable populations. A new unethical study from 1946-48 has been recently uncovered by Susan Reverby. The CDC Director Dr. Thomas Frieden and NIH Director Dr. Francis Collins report on her findings in JAMA, Nov 20, 2010). A copy of Dr. Reverby's forthcoming article is available on her Wellsley College webpage.  I read her amazing history of nursing in America, Ordered to Care: The Dilemma of American Nursing (New York: Cambridge University Press, 1987) when I was an undergrad at the University of Michigan.  I highly recommend this book as it explores the dilemma of a nursing profession that must care for people in a society that 'doesn't value caring.'  There are general lessons there for public health in the US since it remains unclear how the country values public health resources.

4) Potential opportunities to steamline IRB approval. Millum and Menikoff in Nov 16, 2010 Annals of Internal Medicine offer several under-utilized options for improving the efficiency of ethical review.

5) Significant direct (recipient) and indirect (herd immunity) protection secondary to LAIV vaccination of 4-11 year olds was evident even when there was a mismatch between the vaccine and epidemic strains.  (Source: Glezen WP et al JID Dec 1 2010 and Editorial by EB Lewin - both are free full text)

Happy Thanksgiving, safe travels and may your God go with you.

E. coli 0157:H7 and hypertension, renal and cardiac disease

Text-size doesn't correlate with population size

Another not exactly HAI prevention post, but as Mike just told us, we don't have much evidence in ID, so anything can be exciting, no?  This report out of BMJ tells of a May 2000 E. coli O157:H7 and Campylobacter outbreak that arose in the Walkerton, Ontario municipal water system after heavy rainfall drove livestock faecal matter into water supply. The outbreak resulted in 2300 cases of GI illness, at least 27 cases of haemolytic-uraemic syndrome, and seven deaths.  Amazingly, the government created a Walkerton Health Study to monitor individuals for the possible long-term consequences associated with the infection.  After 4-years, there was a 28% increase in hypertension associated with the exposure.  The BMJ report tells of the impact out to 2008.

Overall, people who had acute gastroenteritis were 1.3 times more likely to develop hypertension, 3.4 times more likely to develop both structural and functional renal impairment, and 2.1 times more likely to report a physician-diagnosed cardiac disease. The authors do an excellent job discussing the potential limitations of the study including recall bias and confounding. They also explain away the impact of Campylobacter coinfection by saying that the infectious dose of 0157:H7 is 10 bacteria, while it is 500 for Campylobacter, so people were unlikely to have avoided 0157:H7 exposure.

This is a very unique study.  Most studies that have assessed infections as risk factors for chronic diseases were case-control studies that identified patients with specific outcomes and looked back for certain risk factors.  You would imagine that recall bias would play a much larger role in remembering certain distant and unremarkable exposures like GI illness in a case-control study. With this cohort study, exposures and outcomes were well characterized and measured.  I wonder what this study's impact will be in ascertaining the causes of hypertension, renal and cardiac disease in the general population?  Their recommendation that patients who are post-exposure from E coli 0157:H7 should be carefully monitored for hypertension and renal disease seems prudent.


Clark WF et al. BMJ Nov. 17, 2010 (open access)

Occupational transmission of meningococcal disease

This week's MMWR has a report on transmission of meningococcal disease from an infected patient to a police officer who responded to the patient's home and a respiratory therapist who cared for the patient in the Emergency Department. Neither of the secondary cases were offered postexposure prophylaxis. CDC recommends prophylaxis for HCWs with direct exposure to the patient's oral secretions (e.g., performacne of endotracheal intubation). In this case the police officer was not evaluated for prophylaxis because of a delay in contact tracing. However, the MMWR report admits that if the CDC recommendations were followed the police officer may have not been offerred prophylaxis. What's surprising is that CDC didn't revise the recommendation. Given the severity of meningococcal disease I think we need to be more flexible than CDC's recommendation. We offer prophylaxis to any unprotected HCW within 3 feet of the patient.