9.

2: Searching the Literature

Resource Web site Comment

Cochrane Database A collection of over 4000 systemiatic reviews, it can
of Systematic www.cochrane.org guide not only selection of your topic but can also be
Reviews a source of relevant articles.
Over 600,000 clinical trials of treatment, including
Cochrane Controlled many not found in Medline and Embase. The
www.cochrane.org
Trials Register Cochrane team has included unpublished research and
phase 3 and 4 trials from drug companies.
This is a database that summarizes published
Database of
systematic reviews and meta-analyses, and includes
Abstracts of Reviews
studies of diagnosis, prognosis, and etiology as well
of Effectiveness
as treatment. DARE will also provide you with
(DARE)
examples of systematic search strategies.
This is a bibliographic database that covers more
EMBASE European journals than Medline and has a stronger
pharmaceutical focus.
This is a bibliographic database with a focus on
PsycINFO
psychology and psychiatric illness
This is a bibliographic database with a focus on HIV
AIDSInfo
disease.
This is a bibliographic database with a focus on
AGELINE
geriatrics and diseases of the aged.

There are other potentially useful databases depending on your topic. Ask a medical librarian for
help, as he or she will have knowledge about the available databases, knowledge about search
protocols specific for each database, and experience in clarifying your search strategy. Specifics
on search protocols for each database are beyond the scope of this course. A librarian will also
be able to assist you in getting the full text of the articles as noted above.

Searching Medline for a Systematic Review

Before delving further into the mechanics of searching, it is important to review a few basic
concepts. Medical Subject Heading (MeSH) terms are a very detailed taxonomy of keywords
developed by the National Library of Medicine to describe anything in biomedicine, from "axon"
to "zygomatic arch". In general, it is best to use one of these terms when constructing your
search. This will save you the work of having to think of and search on alternate spellings and
related terms for you topic. The NLM has a MeSH browser at their PubMed site (
http://www.nlm.nih.gov/mesh/meshhome.html) that helps you identify the best term. For
example, when searching on "intrauterine growth retardation", it is important to know that the
corresponding MeSH term is "fetal growth retardation".
Another option when searching is to use words in the title or abstract, also called "free text' or
'text word' searching. This is generally going to give you a broader, more sensitive, but much less
specific list of articles than using the MeSH keywords. For example, searching for the word
"hypertension" in the title or abstract will return every article that uses that word anywhere in the
title or abstract. While some of the articles are relevant, in most hypertension is probably a
comorbidity and not central to the topic of the research article. On the other hand, the MeSH
system is only as good as the people at NLM assigning the keywords. If someone at NLM scans
an article and fails to index the article on a relevant MeSH term, you won't find it if you limit
yourself to MeSH searches.

Boolean logic sounds intimidating, but is really very simple. The terms AND, OR, and NOT are
the most commonly used, and help you craft a search strategy that is either very broad
(sensitive), very narrow (specific) or otherwise optimized to meet your needs. Here is what these
terms mean in English, and how to use them:

Term Example How to use it

AND diabetes AND Only return articles that are indexed on both diabetes and hypertension.
hypertension This makes a search narrower and more specific; articles indexed on one
term but not the other are excluded.
OR diabetes OR Return all articles that are indexed on either diabetes OR hypertension.
hypertension This makes a search more broad and sensitive; articles indexed on either
term, as well as those indexed on both terms, are returned.
NOT diabetes NOT Return all articles indexed on diabetes, but exclude those that are also
hypertension indexed on hypertension. This can be helpful in narrowing your search.
For example, if you are interested in recent articles on the treatment of
Lyme disease only, you may want to use the strategy "Lyme disease
AND 2002(year) NOT immunization" since the literature has been full
of articles on immunization lately. Use ‘Not’ only when absolutely
necessary as you might exclude articles that are relevant to your search.

You can increase your precision by using the proximity operator ADJ (adjacency). Proximity
operators allow you the flexibility to specify how close your terms appear to each other and that
they be in no particular order. In contrast, AND merely requires that both words be somewhere
in the document, while an exact phrase search (you do this by enclosing words in quotes, i.e.
"venous thromboembolism") requires that the terms be next to each other in that exact order.
Two other proximity operators are "With" and "Near". Since the proximity searching terms are
often used synonymously, check the help screen of the database you are searching to see which
ones are used and how. ADJ is the one most frequently used.

Here is an example of using the ADJ proximity operator:

likelihood adj3 returns articles where likelihood and ratio are within 3 words of each other in
ratio$.tw. any order. "adj3" means "adjacent within 3 words", and "tw" is text word
Field Searching

You can narrow your search by specifying which field or fields to search. The fields most often
searched are Title and Abstract. Publication Types is also often searched in MEDLINE. This
will help to avoid retrieving articles or reviews where your term is a co-morbidity or on the
exclusion list. Here are two examples of using field searching:

(sensitivity or returns articles where either sensitivity or specificity appear in the

specificity).ti,ab. title or abstract
practice guideline.pt. returns articles that are labeled as practice guidelines in the
Publication Types field. Used in MEDLINE

Steps in a Good Search

1. List the databases that you plan to search (i.e. Medline, Cochrane Controlled Trials
Register, Cochrane Database of Systematic Reviews, and DARE).
2. Decide whether it is appropriate to limit the search temporally - perhaps it only makes
sense to go back 10 years for a study of the accuracy of computed tomography for
pulmonary embolism, since the technology has evolved considerably since it was first
invented.
3. Decide what kind of study design(s) are acceptable (e.g. only RCTs, or any clinical trial,
or observerational and experimental designs).
4. Write down your research question, i.e. . “How beneficial are insulin sensitizer
medications in patients with diabetes mellitus?”
5. Identify the key concepts in your question. In the example above, those concepts would
be "insulin sensitizer medications" and "diabetes mellitus"
6. Next, think of all the alternate words that could be used for these concepts and write them
down. This includes: synonyms, alternative spellings (British, American, misspellings),
abbreviations, more specific terms (drug name versus drug class), etc. You will want to
note what terms you want to exclude as well. For example, is this search for Diabetes
type II or type I? Insulin dependent or non-insulin dependent? Your list will now look
something like this:

Insulin sensitizer medications Diabetes mellitus

Diabetes Mellitus Type 2 diabetes
Thiazoles NIDDM
Glitazones Diabetes mellitus Type 1
Gliclazide IDDM
Glipizide
Glyburide
Tolazimide
Tolbutamide
Acetohexamide
Carbutamide
 Chlorpropamide
Thiazolidinediones
Rosiglitazone
Pioglitazone
Actos
brl49653
Avandia
metformin
antidiabetic
insulin$

7.
There are several ways to generate your list of search terms – your existing knowledge of
the disease or drug names; looking through the Medical Subject Headings (MeSH)
(http://www.nlm.nih.gov/mesh/meshhome.html); running a preliminary search and noting
the terms used in the titles and abstracts as well as the subject headings assigned, etc.
You will probably use a combination of methods.

Developing your Search Strategy

There are several approaches to developing a search strategy. The one presented here focuses
first on the specificity and then on the sensitivity of the search strategy.

It’s important to make your search specific because it will help you avoid unnecessary work. In
order to do so, first determine what criteria are absolutely necessary for you to accept the article;
that is, you wouldn’t consider any articles that did not meet these criteria. Then, within those
criteria, decide which are either searchable or useful for limiting your search. You will find that
some of your specific requirements, e.g. study duration more than one month, may be involved at
the selection step, but do not translate well into a search strategy. Other criteria, e.g. randomized
controlled trial as a study methodology, can be very useful in narrowing your search strategy.
You may need to discuss this with a librarian who understands the databases you will be
searching.

You can start with the PICO components of your question and determine which are searchable
and which may be spread out into multiple terms. For example, the Population component may
often become multiple search criteria. If you are only interested in hypertensive diabetics, then
hypertension and diabetes are both necessary specific criteria for your review, and they become
two separate concepts in defining your search. On the other hand, outcomes may not be
searchable with specificity and may be dropped from the search strategy, but remember them for
the selection step (i.e. selecting articles for your systematic review). Once you have determined
all of the specific concepts that will be useful for limiting your search, you can combine those
terms with AND as each one of these terms is a necessary component for you to be interested in
an article.

To increase the sensitivity of your search and not miss important information, you want to
consider all the possible “synonyms” for your specific concepts or terms. Consider other names
for the term, such as related names, different disease classifications, British spelling, acronyms
and even sometimes misspellings. Also consider more specific concepts such as specific drug
names and more general concepts such as drug classes. Consider approaching your search both
in text-word form and with MeSH terms. For example, the following terms could all be used to
search for GERD:
gastroesophageal reflux; gastro-oesophageal reflux; GERD; GORD
Once you have decided upon all the terms that you will use to search for a concept, combine
them with OR. For example, you could type a search for GERD as follows:
"gastroesophageal reflux" OR "gastro-oesophageal reflux" OR GERD OR GORD
When you have all of the terms for each concept in your selection criteria, you will combine
them using both AND and OR. For example, a search strategy looking for randomized
controlled trials of hypertensive diabetics developed in this fashion may look like:
(hypertension OR hypertensive) AND (diabetic OR diabetes) AND (RCT OR "randomized
controlled trial" OR "clinical trial")
You can see that search strategies can get long quickly. To save time, consider using truncation.
Truncation (also called wildcards) is the use of a symbol to stand in for a word ending. You type
the beginning or “trunk” of a word and then place a symbol (an asterisk * in Medline) at the end
of the group of letters to retrieve all possible variations. For example, truncating on “child*”
retrieves any word beginning with "child", such as child, children, and childhood.

There are a number of ways to go beyond the initial Medline search strategy. Other databases
have been mentioned above, but your ability to use them may be limited by availability at your
institution. Some may only be necessary for certain questions. Contacting experts in the field is
time consuming, but may be the only way to uncover otherwise unknown information such as
unpublished studies. A basic search strategy for a systematic review is shown below:

1. Search DARE and the Cochrane Database of Systematic Reviews to identify previous
systematic reviews related to your topic, and review their bibliographies.
2. Search Medline.
3. Search the Cochrane Controlled Trials Register on your topic, as it includes many articles
not in Medline and is widely available.
4. Contact experts in the field for unpublished studies.

Note that use of low quality reviews, as an adjunct to your searching, does not lower the quality
of your review.

Optimal Search Strategies

A growing body of research has developed to help optimize search strategies. Researchers have
tried thousands of different combinations of search terms to identify those that are best for
sensitive or specific searches (Haynes, 1995). They are summarized below, using the example of
the term hypertension:

Type of Sensitive Specific

search
Clinical hypertension AND (predict$ OR clinical$ OR predict$.ti. AND rule$ AND
decision rule outcome$ OR risk$) hypertension
Etiology hypertension AND (exp cohort studies OR exp hypertension AND (case-control
risk OR odds (tw) and ratio: (tw) OR relative studies OR cohort studies)
(tw) and risk (tw) OR case (tw) and control:
(tw)))
Diagnosis hypertension AND (exp sensitivity a#d hypertension AND (exp
specificity OR sensitivity (tw) OR diagnosis& sensitivity a#d specificity OR
(sh) OR diagnostic use (sh) OR specificity (tw)) predictive (tw) and value: (tw))
Treatment hypertension AND (randomized controlled trial hypertension AND ((double (tw)
(pt) OR drug therapy (sh) OR therapeutic use AND blind: (tw)) OR placebo:
(sh) OR random: (tw)) (tw))
Prognosis hypertension AND (incidence OR exp mortality hypertension AND (prognosis
OR follow-up studies OR mortality (sh) OR OR survival analysis)
prognos: (tw) OR predict: (tw) OR course: (tw))

Issues to consider if you are retrieving too many articles in your search to be workable:

 Do your “terms” match the terms in the database you are searching?
 Can you find a common “weed” that is clearly not of interest? Adding a NOT criterion to
your search strategy is one way of handling this. For example, if you are interested acute
bronchitis, but have lots of results for acute exacerbation of chronic bronchitis, you could
add a "NOT chronic" term.
 Perhaps you have to narrow your clinical question?
 Maybe too many is not too many. How many of the articles can be easily excluded by a
review of the abstracts? A large retrieval of titles does not require a large retrieval of
articles.

What if no articles (or not enough) are retrieved?

 Do your “terms” match the terms used in the database you are searching?
 Can you determine which search criterion leads to severe limitations? Are these
limitations truly appropriate? What is the best possible answer with knowledge of these
limitations?
 Consider text word searching instead of limiting your search to mesh terms. Use
synonyms and truncation.
 Do you want to broaden your clinical question?
 Do you want to search other databases?
 Find a representative article and search for “related articles” in PUBMED or look at the
mesh headings in that article.
 Ask for help!

Finally, here are some tips if you are a clinician just wanting a "quick and dirty" search for a
clinical question:
 1. Go to the Clinical Queries site in PubMed
2. If a question about treatment, enter the intervention (i.e. "azithromycin" or
"laparoscopy") and the disease (i.e. "acute bronchitis" or "cholelithiasis")
3. Use quote marks to keep words together that belong together. For example, searching
acute and bronchitis as separate words may return "acute exacerbation of chronic
bronchitis" (probably not what you want) while putting quotes around it helps focus your
search
4. Once you find a great article, click on the "Related articles" link to the right of the screen.

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