Getting Help With PubMed

Many librarians turn first to PubMed when they begin a search for the evidence on a clinical question. So how do you learn to effectively use PubMed, brush up your skills, or keep up with the changing interface? Below are some resources to help you do just that:

For Beginners:

Quick Tours: Searching Pubmed - brief, animated tutorials on searching for an author, author and subject, simple subject, or journal.

PubMed Tutorial - Lengthy online tutorial covering basic searching, working with search results, features, MyNCBI, and other topics.

The Basics of MeSH - introduction to Medical Subject Headings

Quick Tours: PubMed's MeSH Database - building a search using MeSH, combining MeSH terms, and applying subheadings. Useful for learning to build a PubMed search using controlled vocabulary.

For More Experienced Users:

Clinical queries using research methodology filters

Special Queries

PubMed Subset Strategies

Search Field Descriptions and Tags

For Keeping Up With Changes:

The NLM Technical Bulletin provides information on changes to MeSH, MEDLINE, PubMed and other resources from the National Library Medicine. The bulletin is published online 6 times per year, and its archives are freely available from 1997-Present.

PubMed New and Noteworthy is an irregularly updated resources with updates on changes to PubMed features. You can read on the page or subscribe through your RSS reader.

General Information from NLM:

PubMed Fact Sheet

MEDLINE Fact Sheet

What's the Difference Between MEDLINE and PubMed?

Big thanks to the National Library of Medicine and NCBI for making these educational resources available!

What is a prodrug?

The Wikipedia entry on colistin notes that colistimethate is an "inactive prodrug of colistin" - this portion of the entry seems to be directly related to this laboratory study by Bergen et al. published in the June 2006 issue of Antimicrobial Agents and Chemotherapy, which reports to be the first study establishing that colistimethate is a prodrug, though this article is not cited in the Wikipedia entry.

Bartleby.com defines "prodrug" as an "inactive precursor of a drug, converted into its active form in the body by normal metabolic processes" (there's also a brief Wikipedia entry on prodrugs) -- the classification of colistimethate as a prodrug by Bergen et al. implies that colistimethate on its own is inactive, but is converted (i.e. metabolized) to colistin after injected into the human body.

This may have significant implications for susceptibility testing - exposing cultured bacteria to colistimethate may provide incorrect estimates of the antibiotic's activity against the bacteria, as conversion within the body to the active form via hydrolysis may be required (Bergen et al. recommend that colistin should be used for these kinds of assays).

As you review the studies published in the literature, this consideration may help you with assessing and critiquing the microbiological assays employed in the studies, as well as any pharmacokinetic and pharmacodynamic investigations. This information would also be key if the initial question about colistin prompted additional follow-up questions such as "How well do microbiological assays perform with respect to colistin sensitivity?" or "How do we determine if we're administering 'enough' colistin to the patient?"

Related link:
The article by Bergen et al. mentions the "Bad Bugs, No Drugs" campaign launched by the Infectious Diseases Society of America, subtitled "As Antibiotic Discovery Stagnates . . . A Public Health Crisis Brews." The campaign includes a white paper, press materials, description of sponsored legislation, and key statistics on the growing problem of antimicrobial resistance among some bacterial strains.

Limitations of review articles

In the October case study, we briefly discuss the relevance and quality of a small sample of general review articles for the clinical question we were trying to answer.

Review articles are viewed by many clinicians as a quick and easy "surrogate" for the primary data on a given topic, but are subject to tremendous variability in quality and in relevance to a specific clinical question. Often written by one or two "experts" in a field, the review articles are subject to potential bias, including the influence of the authors' personal viewpoints, gaps in literature searching practices that may lead to the omission of relevant research, errors in the translation of data from the primary literature to summarization in the review, misrepresentation or misinterpretation of original source data -- problems that are difficult for a reader to identify without seeking out the primary literature to verify the review's recommendations and conclusions.

In 1999, McAlister et al considered this issue in their study in the Annals of Internal Medicine, "The medical review article revisited: has the science improved?" (PDF). Examining compliance of reviews from 6 major medical journals with 10 quality criteria (e.g. "The methodologic validity or quality of the included studies was assessed"), the authors noted "Of 158 review articles, only 2 satisfied all 10 methodologic criteria (median number of criteria satisfied, 1)."

A JAMA article in 2002 by Rochon et al compared review articles in peer-reviewed journals to those in "throwaway" publications using a quality assessment instrument developed by Barnes and Bero, finding great variability in article quality. The authors note, "mean (SD) quality scores were highest for peer-reviewed articles (0.94 [0.09] for systematic reviews and 0.30 [0.19] for nonsystematic reviews) compared with throwaway journal articles (0.23 [0.03], F2,391 = 280.8, P<.001)" (higher number translates to higher percentage of quality criteria met). Thus, variability in quality measures was revealed not only for trade publications, but also for articles published in major peer-reviewed outlets such as the Annals of Internal Medicine, JAMA, Lancet, and others.

What implications does this have for our searching, selection, and summarization practices? In the current case, we thoroughly consider the primary data first, and then move to an examination of the review items - our thorough understanding of the body of data discussing colistin and its derivates for treatment of antibiotic-resistant Gram-negative pneumonia allows us to critique the review articles and note any omissions or issues in these items.

One of our most basic skills as librarians also can inform this assessment process -- given our comprehensive searching practices, do the authors of the review articles describe how they identified the studies they included? Do they cite references to support key statements and recommendations? Do their reference lists seem to be in line with what we are seeing in our search results, and are they current? Do they include tables or other illustrations that summarize the individual studies in greater detail? Are their inferences in line with our intuitive understanding of the literature?

Consideration of questions such as these can help us assess the quality and relevance of a review article, as well as aid us with identifying instances in which a review article should be accompanied by a few words of caution, supplemental primary data, or omitted completely due to our serious concerns about its methods and/or conclusions. By "filtering" the review literature in this way for clinical questions, we make great use of our skills and strengths as information experts.

Refining clinical questions for more effective and relevant search results

The level of detail in an information request from a user, whether in received in-person the library, by email or telephone, or on clinical rounds, is not always as high as we might like. If the question is imperfectly defined or lacks clarity in intent, it can be very difficult to be certain that you are retrieving the "right" information from the literature, which also will likely cause problems to the requestor if he/she receives results that differ from the situation tthe information was intended to address. If you receive a fairly broad question, how do you refine the question?

Some have suggested the PICO format (Patient or Problem, Intervention, Comparison, Outcome) as one means of refining a clinical question (more information on PICO at bottom of post).

Consider this situation -- the question in the current case study may have originally looked something like "When should colistin be used in the intensive care unit?" How well does this question fit into the PICO format?

Patient/Problem: ICU patients
Intervention: colistin
Comparison: not defined
Outcome: not defined

If you received this question on the reference desk from the clinician treating the patient considered in the case study, rather than on bedside rounds where you'd be hearing the details of the situation and would have a better idea of why colistin is being debated, how would you work with the user to refine this query?

From a searching perspective, it seems as if the Patient/Problem portion of this query may be a key initial target for refining this question. There are a multitude of reasons why a patient might be in the ICU, but a somewhat more limited list of reasons why a clinician might consider administering an antibiotic such as colistin. We know that, because of the increasing problems of antibiotic resistance, particularly in the intensive care setting, clinicians are working to reserve antibiotic administration for situations in which it is truly needed. Asking the requestor a brief question such as "What conditions might you consider treating with colistin in the ICU?" would likely be very useful in understanding this question in the absence of additional patient details.

You also may quickly query the user considering the Comparison and Outcomes elements of the format: "Are you weighing colistin against another treatment option?" and "Are there particular outcomes are you particularly interested in (e.g. radiologic confirmation of infection resolution, mortality, morbidity, ventilator days, length of stay)?"

Refining the question to include a focus on Acinetobacter pneumonia in this case improves the search results dramatically.

A PubMed search based on the initial, broad question may look something like, retrieving about 90 citations:

(colistin OR colistimethate) AND (critical care OR intensive care OR intensive care unit OR critical illness OR ICU) (link to these search results)

Focusing on patients with Acinetobacter pneumonai using the strategy employed within this month's case leads to this strategy, retrieving about 30 citations:

colistin[mh] OR colistin[tiab] OR colistin[substance name] OR colistimethate[tiab] OR colistimethate[substance name]) AND (Acinetobacter[mh] OR Acinetobacter infections[mh] OR Acinetobacter[tiab]) AND (pneumonia[tiab] OR pneumonia[mh]) (link to these search results)

The first search fails to retrieve approximately two-thirds of the citations retrieved by the search focused on Acinetobacter pneumonia, a striking lack of overlap that may have a significant impact on the search results you might provide the requestor with. Refining the query with a few quick follow-up questions for the clinician can enable a much more productive and efficient, and likely much more relevant, searching process.


A few additional resources considering the use of PICO for clinical question refinement:
- A group of library and information sciences students from the University of British Columbia have drafted a few graphical representations of this structure that may be useful in picturing how this format might be used in structuring and refining a search query (via Dean Giustini's Google Scholar blog).

- The National Library of Medicine also has developed an interface for searching PubMed that operationalizes this format.

- An article by Booth, O'Rourke, and Ford (Bull Med Libr Assoc. 2000 July; 88(3): 239–246) discusses the impact of PICO structure use on the pre-search reference interview, including a form for mediated search requests based on PICO elements.

- The Univerity of Washington's HealthLinks has a very practical guide for translating clinical questions into PICO format, complete with practice questions.

Updating the October case study's search results

I just reviewed the search retrieval in PubMed today for the case, and saw that there are a few new citations that may be of interest for updating the case. I've included a few notes below considering the relevance of each of these potential additions to our literature summary on this clinical question.

New reference #1: Falagas ME, Kasiakou SK, Kofteridis DP, Roditakis G, Samonis G. Effectiveness and nephrotoxicity of intravenous colistin for treatment of patients with infections due to polymyxin-only-susceptible (POS) gram-negative bacteria. Eur J Clin Microbiol Infect Dis. 2006 Sep;25(9):596-9. (PubMed record)
The first author in this study was involved in two of the review articles represented in the October case and one of the studies; this new article is a prospective case series including 27 patients with resistant Gram-negative infection treated with IV colistin. The authors indicate that the infection was pneumonia in 9 patients, who received inhaled colistin in addition to IV drug. The authors note "[i]n-hospital mortality and clinical response were 15% and 85%" and observed nephrotoxicity in 2 patients during the study. This article would be a good addition to the literature summarized in the October case for its inclusion of prospective primary data on efficacy and adverse effects of colistin in a patient population directly relevant to the patient situation we considered in the case.

New reference #2: Saballs M, Pujol M, Tubau F, Pena C, Montero A, Dominguez MA, Gudiol F, Ariza J. Rifampicin/imipenem combination in the treatment of carbapenem-resistant Acinetobacter baumannii infections. J Antimicrob Chemother. 2006 Sep;58(3):697-700. (PubMed record)
This is a small prospective study of 10 patients with Acinetobacter infection, examining rifampicin/imipenem as a possible alternative to colistin, finding that this antibiotic combination was not effective in treating resistant Acinetobacter infections (somewhat relevant, in ruling out an alternative therapeutic strategy) .

New reference #3: Linden PK, Paterson DL. Parenteral and inhaled colistin for treatment of ventilator-associated pneumonia. Clin Infect Dis. 2006 Sep 1;43 Suppl 2:S89-94. (PubMed record).
This is a new review article that discusses that efficacy of colistin for treating VAP, synthesizing 5 studies on the topic (including studies that examined inhaled rather than IV administration of the agent) and noting the incidence of colistin-induced nephrotoxicity ranging from 8-36%. This current review would likely serve as an update and replacement to the Jain and Danziger review covered in the October case.

These new references also point out that this is a developing topic; ongoing surveillance of the literature would be a useful proactive step for the librarian in this case, aiding the team with understanding the evidence as the literature evolves and maintaining clinical practices in line with the most current research data.

Comments feed added

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Thanks to FreshBlog for tips on establishing this feed.

We look forward to hearing your questions and comments as the blog evolves!

Wikipedia in a health sciences context

To continue with the topic of locating and assessing background resources for the clinical question, it may be useful to explore the appropriateness of a resource such as Wikipedia. The relevance and quality/reliability of Wikipedia entries are issues that are likely of central interest to the larger health sciences library community. This clinical case presents an opportunity to take a look at the type of medical information present in Wikipedia. To get a quick snapshot, let’s look at the first five medical concepts presented in Table 1 of the case study.

Respiratory failure -- this entry is a stub, i.e. “too short to provide encyclopedic coverage” of the topic. The entry describe two types of respiratory failure, causes, and one sentence on treatment. While the entries that are linked to for the causes tend to be fairly lengthy and descriptive, with links to external references, this particular entry is not clinically useful as the information presented is sparse and not clinically detailed.

Ventilator-associated pneumonia (VAP) – a more in-depth entry than Respiratory Failure, discussing the symptoms and signs, diagnosis, pathophysiology, microbiology, treatment, prevention and epidemiology and prognosis of VAP. For the purposes of background reading to understand this medical concept, there seems to be enough information to obtain a clear "picture" of the condition. Ideally, we might prefer to see more external references than just the ATS/IDSA Guidelines, but these guidelines are a concrete start. Also, the guidelines are available with free full-text online, but that link is not yet included in the entry. Interestingly enough, the last change made to the article as of this posting was removing its status as a stub. Quite a difference between the respiratory failure and this one.

Acinetobacter – the length of this entry is between that of the entry for respiratory failure and that for VAP. The entry describes at the basic level the identification, description, and treatment for the organism. The treatment section does state the success of colistin for treatment, it but no external reference is provided for independent verification. One section of the entry is marked as needing considerable re-write. Two of the references listed link to PubMed.

Chronic Liver Failure w/ Hepatic Encephalopathy – The entry for Liver Failure is two paragraphs long, with four references provided. It clearly lacks the needed information in context to the clinical question. Not categorized as a stub, but perhaps is should be?

Typing in “chronic liver failure” leads the user to the “Liver Failure” entry discussed above; there is also a separate entry for hepatic encephalopathy. The HE entry fares somewhat better in a quick evaluation than some of the other entries - this entry is accurate in its description of the condition; however, only pathogenesis, grading and treatment are briefly covered. The latest substantive edit was in February 2006 to correct a statement on the effectiveness of lactulose, and a reference is provided. However, the very next paragraph indicates the decline of the use of Neomycin, with no external references to support the statement.

Bronchoscopy - - the importance of the bronchoscopy for this case is essentially to understand the basics of the procedure if unfamiliar, and this entry meets that need. While the entry is not lengthy, it is of sufficient details to understand the aspects involved – including a link to an image from a public-domain website. And look! The references include a link to MedlinePlus articles.

Preliminary conclusions: Even this brief snapshot of Wikipedia has utility for understanding the issues involved in a resource that allows anyone to edit the content. These issues are commonly heard when the topic of Wikipedia arises, and in the particular context of medicine - unsupported statements, widely varying level of detail, and problems with clinical relevance or direct applicability to clinical questions, such as the one explored by this case, will need to be carefully considered.

Your thoughts?

Additional general commentary on Wikipedia:
- "The Faith Based Encyclopedia," written by a former Brittanica editor-in-chief

- "Internet Encyclopedias Go Head to Head," from Nature; this has been disputed and fairly widely discussed online

- "Can Wikipedia conquer expertise?," from the New Yorker

Background Resources for October 2006 Case

Table 1 of our current case lists several medical concepts which are central to our clinical question. This post is intended to explain why each concept is important, how to assess the quality and relevance of background information sources, and to provide links to freely available resources may be useful for acquiring background knowledge on these topics. You may also wish to consult textbooks, databases, or other subscription items available at your own library.
The Question:
What is the evidence basis for the use of intravenous colistin for multi-drug resistant Acinetobacter infections in the adult, non-neutropenic, critical care population?

How to Evaluate Online Resources:

Medical Library Association: A User's Guide to Finding and Evaluating Health Information on the Web

MedlinePlus: Guide to Healthy Web Surfing

National Center for Complementary and Alternative Medicine: 10 Things To Know About Evaluating Medical Resources on the Web

National Cancer Institute: How To Evaluate Health Information on the Internet: Questions and Answers

U.S. Food and Drug Administration: How to Evaluate Health Information on the Internet

The Concepts:
Respiratory Failure
The patient was admitted to the ICU with respiratory failure; this informs you that the patient is currently unable to breathe on his own, resulting in the use of mechanical ventilation and leading to the development of ventilator-associated pneumonia (VAP).

eMedicine: Respiratory Failure

The Merck Manuals Online Medical Library, Home Edition: Respiratory Failure

MeSH Database: Respiratory Insufficiency

Ventilator-Associated Pneumonia
The patient is showing signs of VAP, which is why the cultures (brochoscopy and bronchoalveolar lavage) were conducted, leading to the identification of the Acinetobacter species in this patient.

CDC: Ventilator-Associated Pneumonia

MeSH Database: Pneumonia, Bacterial; Respiration, Artificial; Ventilators, Mechanical

Acinetobacter
This is the organism identified as causing the patient's pneumonia, and you've been asked to find evidence on drugs to treat this specific type of infection.

CDC: Drug Resistant Acinetobacter Infections in Healthcare Settings

eMedicine: Acinetobacter

MeSH Database: Acinetobacter

Chronic Liver Failure with Hepatic Encephalopathy
This is the other condition (in addition to respiratory failure) for which the patient was admitted to the ICU. It may or may not turn out to have an impact on the drug regimen the patient receives, but helps you understand the overall clinical picture for this patient. Hepatic encephalopathy is the underlying cause of the patient's respiratory failure, as it leads to decreased mental status which in turn causes respiratory dysfunction and the inability of the patient to protect his own airway. The resources listed below address hepatic encephalopathy, but we don't know the cause or type of the chronic liver failure.

MedlinePlus Medical Encyclopedia: Hepatic encephalopathy

eMedicine: Encephalopathy, Hepatic

MeSH Database: Hepatic Encephalopathy; Liver Failure

Bronchoscopy
The patient underwent bronchoscopy when signs of VAP developed. Bronchoscopy is a fairly common procedure, so it will help you in the future to understand this term.

MedlinePlus Medical Encyclopedia: Bronchoscopy

UpToDate Patient Information: Fiberoptic Bronchoscopy

MeSH Database: Bronchoscopy

Bronchoalveolar Lavage
The procedure is used with bronchoscopy to identify the infectious organism affecting a patient. "Lavage" essentially means "to wash," and has its origin in the Latin lavare - the lungs are washed with fluid, which is then suctioned back up for culturing and diagnostic purposes.

MeSH Database: Bronchoalveolar Lavage

Wikipedia: Bronchoalveolar Lavage - Normally, you might want to consult other, more authoritative background resources before checking Wikipedia, but there is very little basic information on this procedure online. In this case, reading the Wikipedia entry can give you a basic idea of what bronchoalveolar lavage consists of.

Antibiotic Sensitivity/Susceptibility Testing
This type of testing is used to determine which agents will be effective against an infectious organism. It is how doctors know what the "right" antibiotic is to use for an infection.

Lab Tests Online: Susceptibility Testing

MeSH Database: Microbial Sensitivity Tests

Colistin
Colistin is an antimicrobial (or antibacterial) drug, and the clinicians would like to know if it has been proven effective against Acinetobacter infection. A search of free resources does not turn up much of anything on this drug. However, through further investigation, we find that Colistimethate is a derivative of Colistin, and information is available on that.

MeSH Database: Colistin

MedlinePlus Drug Information: Colistimethate Injection

Have other suggestions for background resources? Post them in the comments.