More on C. difficile

Clostridium difficile was featured on the Adopt a Microbe blog a few days ago. The blog is written by an Australian medical student, Emma Lurie, and for each post she includes a cartoon drawing and few key facts about the microbe. A quick fun way to learn about the featured pathogen.

How does antibiotic resistance develop?

October's case study looked at figuring out the best treatment options for an increasingly antibiotic-resistant organism causing pneumonia in an ICU patient. A recent article in the Washington Post, "FDA Rules Override Warnings About Drug," includes a great graphic illustrating how antibiotic resistant bacteria develop.

The article is one of many responses from the popular media and the scientific community about the pending approval by the FDA of the use of cefquinome, a 4th generation cephalosporin antibiotic, in cattle, and the potential and very likely increase in bacterial resistance associated with using this antibiotic more widely.

The basic idea is that you use the antibiotic in cows, the bacteria in those cows starts developing resistance, and then that resistance is transmitted to humans when they consume beef contaminated with the resistant organisms (the biggest two would be E. coli and Salmonella spp.).

A FDA panel met in Sept 2006 to discuss risks and benefits of approval for this agent, and the slides from the session provide more information on risks, benefits, how cefquinome works, etc.

(spotted via Mike the Mad Biologist)

What makes a "good" case report?

The discussion of case reports in the current JMLA case study focuses on the relevance of the cases to the question being examined. What else should you consider in evaluating the "quality" of a case report?

As mentioned in a previous post about the new Journal of Medical Case Reports, case reports serve a number of key functions in understanding disease diagnosis and therapy, as well as potential side effects of diagnostic or therapeutic interventions.

A good case report tells the "story" of a particular patient's case (or a small group of patient's case), in a temporal sequence and with enough detail to describe for the reader how the case unfolded, what diagnostic tests and/or therapies were employed, the process of differential diagnosis, and the outcome of the case.

Case reports are generally narrative, but are still subject to the basic principles of the scientific method -- they must tell us how the authors went through the process of understanding what was "going on" in the patient's case, how the patient was evaluated and treated, and what the outcome was, all the while stressing the "evidence" for the authors' conclusions. A case report provides a real-world example of how clinicians formulate and test hypotheses in a clinical scenario.

In their instructions for medical students interested in drafting case reports, Anwar et al. advise that a case report "should read like an interesting story, which your reader should enjoy." (How to write a case report, Student BMJ, 2004 Feb, 12:60-1.) . These authors recommend a case report format that includes an introduction, the case itself (history, clinical features, investigations, treatment and outcome, progress of the case), discussion with literature review, key message the report is trying to convey, and any recommendations based on the authors' experience with the case.

In looking at the cases for this month's question, there is some variability in the amount of detail provided (e.g. some articles report how long the patient had the ileostomy before diarrhea developed while others don't). Sorinola et al examined instructions for authors from 163 core medical journals that publish case reports, and note that the journals' instructions generally focused on style (which sections the case should be divided into, how many illustrations were allowed) rather than content (originality, instructive content, innovation, unusual/rare disease). Interestingly, instructions noted the role of a case report for hypothesis generation in only 9 of the titles (6%). Table 2 of this study also includes a suggested checklist for case report content, based on the investigators' examination of journal instructions to authors, that may also be useful in evaluating case report content:

Reference: Sorinola O, Olufowobi O, Coomarasamy A, Khan KS. Instructions to authors for case reporting are limited: a review of a core journal list. BMC Med Educ. 2004 Mar 25;4:4. (PubMed record with link to full-text in PubMed Central)

One basic question likely underlies any evaluation of a case's relative quality for a particular topic: Does the case provide enough detail, organized appropriately, to understand the steps that the author too, in evaluating and treating the patient, and the eventual outcome/prognosis for the case? For the C. difficile question explored in this month's case study, a good case report would then include:
- a discussion of when the ileostomy was placed and when the diarrhea developed
- description of the patient's immediate history around the time the persistent diarrhea developed (e.g. recent antibiotic therapy); in-patient vs. out-patient development of symptoms?
- duration of the diarrhea and volume of output from the ileostomy
- differential diagnosis - did the authors suspect issues other than C. diff infection? How did they arrive at the diagnosis of C. diff as a causative organism?
- treatment and outcome, including antimicrobial therapy, any operative intervention required, prevention of complications of diarrhea, how long it took the symptoms to resolve, length of hospital stay, any associated complications, final outcome of the patient case

And finally, for a question like this for which the evidence seems quite rare, the authors' connection between their case and related literature on the topic (with possible review of reported cases) proves very useful in verifying that your literature search was effective in identifying all of the relevant literature.

Related links:
- Judging criteria from a Navy student case report competition (links to Word document) -- another suggested format for case report structure, with guidance in how to assess quality for each section
- Ch. 10: Case reports etc., excerpt from Iles's Guidebook to better medical writing -- suggestions for authors interested in publishing case reports

Cases in context: levels of evidence

In thinking about how case reports "fit in" to the types of evidence available to answer clinical questions, I thought it might be useful to do a quick "refresher" post on the kinds of literature available.

Many also turn to a graphic to represent how the levels of evidence all fit together, in terms of relative strength of methodology (e.g. this evidence pyramid developed by the University of Washington Health Sciences Libraries, which was in turn adapted from this pyramid by the University of Virginia Health Sciences Library).

If you search for "evidence pyramids" or levels of evidence you'll find there's a little bit of "wobble" in how these are constructed -- the various authors arrange some of the levels differently, particularly at the bottom end of the pyramid.

So, the levels of evidence in roughly a hierarchical order, in broad categories, starting at the top and working our way down (with links to additional definition):

Summing/collating the "best" evidence (methodological rigor, relevance)
- systematic reviews and meta-analyses (also see "How to read a paper: Papers that summarise other papers")

- practice guidelines; consensus statements authored by groups of experts (e.g. NIH Consensus Development Program)

Primary literature, i.e. the evidence from actual clinical studies
- randomized clinical trials

- prospective or retrospective cohort studies; case control studies

- other observational studies (e.g. ecologic studies, cross-sectional designs)

- case series; case reports; reviews of reported cases (a case report or case series with a summary of other cases reported in the literature, usually accompanied by a table summarizing these other cases, e.g. this article from The Oncologist)

Though this is a rough approximation of how these types of evidence fit together in terms of relative quality, there are serious problems with looking at these levels as "absolutes" - the stated study design or article type provides only a rough indicator of potential quality; the true quality of a given study/article depends on the design, execution and reporting of the study in the paper, as well as how relevant it is to the question at hand.

Coming soon - We'll continue this discussion, considering strengths and weaknesses of each type of evidence, and where other kinds of literature fit in (e.g. traditional review articles, structured abstracts plus critique, textbooks, letters to the editor, etc.)...