Pharmacology Journal Club Talk

by Mick Draper May 2011

Variability in the P-glycoprotein drug transporter and its influence on immunosuppressant (Tacrolimus) efficacy and safety in renal transplant patients.

A logic grid is useful to sort out the language and logic needed to produce a good search strategy.
You can produce a logic grid on the back of an envelope, but I think that it's useful to use Word or any other program that has a table feature so that you can save your grid to use later if you want to revise your search.

There are 4 concepts here.
I begin with a grid of 4 concepts

Now to find subject headings, synonyms, or alternative terms for these concepts.

I like to begin with PubMed because it includes a standardised set of subject headings that goes back a long way, and an excellent search engine.

PubMed

PubMed citations come mostly in 3 types

[As supplied by publisher]
[in process]
[indexed for MEDLINE]

It's useful to search using MeSH because this should find most of the citations in the database that are on a particular concept.
It's also useful to search for articles that don't have MeSH added as these are usually the most up to date.

I begin in the MeSH database looking for p-glycoprotein.
I'm not looking for p-glycoprotein drug transporter or even the concept of drug transporter because I've already established that there is no subject heading for drug transporters.

PubMed
I open the PubMed database from the Library home Quick Links.

MeSH Database
You can find subject headings by using the MeSH Database.

Type in one concept at a time, and it's best to use the term that is most often used in the literature.
Click on the Search button.

The MeSH database finds 10 subject headings. The first two look promising, especially the first one.
Most MeSH come with a definition which can help to sort out whether it's appropriate

I click on the link to P-Glycoprotein.
Notice that MeSH sometimes come with subheadings.
I'll talk about these later.

I scroll down the screen to find where this MeSH appears in a hierarchy of related MeSH.

Now that I've confirmed p-glycoprotein as a MeSH I can add it to my logic grid.
Adding [mh] to the phrase p-glycoprotein would mean that PubMed will search for the term only as a subject heading.
I also want to search for this term where it appears in titles, abstracts, and other useful areas of each citation.

I'll demonstrate a search of the PubMed FAQ to show [tiab] and [tw].

Because p glycoprotein doesn't have more specific headings listed below it, I can search for it as a MeSH and in the titles, and abstracts of citations as a text word.

If I look at the Entry Terms in the MeSH database I might find some synonyms or alternative terms for this concept.

I can add these terms to the logic grid with [tw]

I'll look at the MeSH for tacrolimus next.

Again this concept is at the bottom of the hierarchy and so we can use [tw] as the field tag.
There are several other terms listed in the Entry Terms.

I've also added the terms for the concept of renal transplant as well.

Notice that I've used * in the second and third columns.
This is the truncation symbol in PubMed and most other databases.

Searching renal transplant* will let me find

renal transplant OR renal transplants OR renal transplantation OR renal transplantations etc

I've decided that the final concept includes either efficacy or safety.
These terms are a bit trickier.

Here's the MeSH for Safety.

The MeSH Safety has a more specific term listed below it in the MeSH hierarchy.
If I search for Safety[mh] then I'll also search the subject heading Safety Management.

Because I also want to search safety and safe etc as text words I'll include both safety[mh] and safe*[tw] in the logic grid.

Now comes the slightly trickier bit because there are other terms that have to do with safety that don't appear on this MeSH screen.

I think it would be worth searching treatment outcome as an alternative term for safety.
Treatment outcome turns out to be a MeSH, so I'd like to include this in the logic grid along with outcome*[tw]

Now I'd like to add subheadings that have to do with safety.

adverse effects[sh]
administration and dosage[sh]
standards[sh]

Because [tw] covers subheadings then I could choose to use this tag instead of [sh].
This would mean an increased chance of finding [as supplied by publisher] and [in process] citations.

I could have used the subheadings added to MeSH such as p-glycoprotein/adverse effects[mh], but I prefer to add them as floating subheadings so that they can be associated with any appropriate MeSH such as p-glycoprotein, tacrolimus or kidney transplantation

Logic Rules
Now the logic grid becomes very useful for formulating the search to go into PubMed.
All the terms that are in the same column are joined using OR logic.
All the terms joined by OR logic are enclosed in round brackets.

I'll demonstrate the reason for the brackets

This search can now go into the PubMed database.

How does this result compare with the 'naive' search

p-glycoprotein AND tacrolimus AND renal transplant AND (efficacy OR safety)

Clinical Queries
PubMed has some software that tries to limit searches to clinical citations.
This is often worth using as long as you're not expecting to find everything on a topic.
I click on Advanced Search.

I scroll down the screen and click on Clinical Queries.

Study types
I've designed some PubMed searches for different sorts of study types such as cross sectional studies and cohort studies, as well as including links to expert searches for randomised controlled trials and systematic reviews.
You can click on any of the study types and then AND in your subject search to find citations on your topic with the appropriate study type.

Study Type link

Using the Abstract display will allow me to find those citations that have links to the online full text articles.
There are two sorts of these articles, those that are free, and those that are covered by The Uni of Adelaide Library's subscriptions.

Access to online full text is through the Uni of Adelaide Online icons.

If there isn't a Uni of Adelaide Online icon don't give up.
Check the full title of the journal in which the article appears by hovering your cursor over the abbreviated title.

Look for this journal title in the Library Catalogue or Summon.

If the Library really doesn't have the article, postgrads and staff can make up to 50 interlibrary requests for articles each calendar year without cost.

Now you can select citations to add to EndNote or other bibliographic management software.

You can view similar citations by clicking on the Related citations links.

You can limit your search by date, language, and other options but you should be warned that most of the Limits are MeSH and if you use them you will lose your in process and as supplied by publisher citations.

MyNCBI allows me to save searches and create email alerts.
New users of MyNCBI have to register and wait for their registration to take effect before saving.

Details of how to do this are available here Saving Searches and Creating E mail Alerts.

A few other things about MeSH
There are subject headings that can include drugs and other substances.
We'll look at the MeSH for opioid analgesics.

Notice that this MeSH turns up under three separate subject 'branches'.

Pharmacological Action [pa]
Substances known to have a particular pharmacologic action. Each pharmacologic action term index is created with the drug/substance terms known to have that effect. This includes both MeSH terms and terms for Supplementary Concept Records.

Supplementary Concept [NM]
Includes chemical, protocol or disease terms. Synonyms to the Supplementary Concepts will automatically map when tagged with [nm]. This field was implemented in mid-1980; however, many chemical names are searchable as MeSH terms before that date.

The MeSH for opioid analgesics seems well short of being comprehensive.

Embase.com
Embase is published by Elsevier and is a subscription database.
PubMed and Embase should both be used to get most of the citations to significant articles.

Embase has a reputation for covering many more articles on drugs than PubMed, and allowing more specific searching on drug topics.

Embase searches part of PubMed at the same time as searching Embase.

One of the things Embase does better than PubMed is providing more synonyms for subject headings.

Here's a search for opioids as a subject heading.

Opiate is a more specific Emtree term under narcotic analgesic agent, and so is included in any exploded search.

Sex differences in opioid-alcohol interactions

First I look for sex differences in Emtree

If my preferred term doesn't come up I can try another term or what I usually do is search for my term in the titles of citations and then look at how these citations are indexed.

I use Advanced search which allows me to use field tags to specify that the search should be made only in the title field.
Note that there is a drug search option.

When searching in Embase phrases have to be enclosed in single or double quotes.
To restrict searches to a particular field use a full colon : and then the field tag.

I usually check several citations to make sure that the Emtree terms are consistent.
Now I can search this term in Emtree.

I look at the definition to make sure this is the term I want.

Because there are no other terms listed below then I don't need to explode the search. I can add it to the logic grid to be searched as a descriptor, in the title, or in the abstract of citations.

The synonyms suggest other terms to search in titles and abstracts.

drug alcohol interaction is an Emtree term so I can combine it with the terms in column 3

I find it easier to do the searches from each column separately and then combine them.

('sex difference':de,ab,ti OR (sex NEXT/1 difference*):ab,ti OR (sex NEXT/1 dimorphism*):ab,ti OR (sexual NEXT/1 dimorphism*):ab,ti OR (sex NEXT/1 factor*):ab,ti)

('narcotic anelgesic agent'/exp OR opioid*:ab,ti OR opiate:ab,ti)

('drug alcohol interaction':de OR alcohol:de,ab,ti OR ethanol:ab,ti)

Drug Searches in Embase

Click on the Drug search tab.

You can select a wide range of subheadings and routes of administration