Medical prescription

The prescription symbol, ℞, printed on the blister pack of a prescription drug manufactured in the Philippines.

A prescription is a health-care program implemented by a physician or other qualified health care practitioner in the form of instructions that govern the plan of care for an individual patient.[1] The term often refers to a health care provider's written authorization for a patient to purchase a prescription drug from a pharmacist.

Format and definition

The format of a prescription falls in to seven parts. However, with modern prescribing habits, some are no longer applicable or included on an everyday basis.

Definition: For such prescriptions to be accepted as a legal medical prescription, it needs to be filed by a qualified dentist, herbalist, nurse, pharmacist, physician, veterinarian etc., which falls within their remit to prescribe such treatments. This is regardless of whether they included controlled substances or freely available over-the-counter treatments.

Prescription symbol U+211E PRESCRIPTION TAKE (HTML ℞)

Prescriptions may be entered into an electronic medical record system and transmitted electronically to a pharmacy. Alternatively, a prescription may be handwritten on preprinted prescription forms that have been assembled into pads, or printed onto similar forms using a computer printer or even on plain paper according to the circumstance. In some cases, a prescription may be transmitted from the physician to the pharmacist orally by telephone; this practice may increase the risk of medical error. The content of a prescription includes the name and address of the prescribing provider and any other legal requirement such as a registration number (e.g. DEA Number in the United States). Unique for each prescription is the name of the patient. In the United Kingdom and Ireland, the patient's name and address must also be recorded. Each prescription is dated and some jurisdictions may place a time limit on the prescription.[2] In the past, prescriptions contained instructions for the pharmacist to use for compounding the pharmaceutical product but most prescriptions now specify pharmaceutical products that were manufactured and require little or no preparation by the pharmacist. Prescriptions also contain directions for the patient to follow when taking the drug. These directions are printed on the label of the pharmaceutical product.

'℞' is a symbol meaning "recipe". It is sometimes transliterated as "Rx" or just "Rx". This symbol originated in medieval manuscripts as an abbreviation of the late Latin verb recipere, specifically the second person singular imperative form recipe meaning "take", thus: "take thou".[3] Originally abbreviated Rc, the c was simplified and finally written as a straight stroke making it look like an x in combination with the right "leg" of R. Medieval prescriptions invariably began with the command to "take" certain materials and compound them in specified ways.[4]

Folk theories about the origin of the symbol '℞' note its similarity to the Eye of Horus,[5][6] or to the ancient symbol for Zeus or Jupiter, (), gods whose protection may have been sought in medical contexts.[7]

The word "prescription", from "pre-" ("before") and "script" ("writing, written"), refers to the fact that the prescription is an order that must be written down before a compound drug can be prepared. Those within the industry will often call prescriptions simply "scripts".

In certain states medical marijuana legislation has been drafted calling for a health care professional's written or oral "recommendation", in the belief that a written one would be legally distinguishable from a prescription, but since written advice to a patient is what a prescription is, that belief is mistaken. Jurisdictions may adopt a statutory definition of "prescription" that applies as a term of art only to the operation of that statute (see below about prescriptions that may legally be filled with prescription-only items), but the general legal definition of the word is this broad one.

Contents

In some countries, drug companies use direct-to-prescriber advertising in an effort to convince prescribers to dispense as written with brand-name products rather than generic drugs.

Many brand name drugs have cheaper generic drug substitutes that are therapeutically and biochemically equivalent. Prescriptions will also contain instructions on whether the prescriber will allow the pharmacist to substitute a generic version of the drug. This instruction is communicated in a number of ways.

In some jurisdictions, the preprinted prescription contains two signature lines: one line has "dispense as written" printed underneath; the other line has "substitution permitted" underneath. Some have a preprinted box "dispense as written" for the prescriber to check off (but this is easily checked off by anyone with access to the prescription). Other jurisdictions the protocol is for the prescriber to handwrite one of the following phrases: "dispense as written", "DAW", "brand necessary", "do not substitute", "no substitution", "medically necessary", "do not interchange".[8] In other jurisdictions they may use completely different languages, never mind a different formula of words. In some jurisdictions, it may be a legal requirement to include the age of child on the prescription.[9] For pediatric prescriptions some advise the inclusion of the age of the child if the patient is less than twelve and the age and months if less than five. (In general, including the age on the prescription is helpful.) Adding the weight of the child is also helpful.

Prescriptions often have a "label" box.[10] When checked, the pharmacist is instructed to label the medication and provide information about the prescription itself is given in addition to instructions on taking the medication. Otherwise, the patient is simply given the instructions.

Some prescribers further inform the patient and pharmacist by providing the indication for the medication; i.e. what is being treated. This assists the pharmacist in checking for errors as many common medications can be used for multiple medical conditions.

Some prescriptions will specify whether and how many "repeats" or "refills" are allowed; that is whether the patient may obtain more of the same medication without getting a new prescription from the medical practitioner. Regulations may restrict some types of drugs from being refilled.

In group practices, the preprinted portion of the prescription may contain multiple prescribers' names. Prescribers typically circle themselves to indicate who is prescribing or there may be a checkbox next to their name.

Writing prescriptions

Who can write prescriptions (that may legally be filled with prescription-only items)

National or local (i.e. state or provincial) legislation governs who can write a prescription. In the United States, physicians (either M.D., D.O., or D.P.M.) have the broadest prescriptive authority. All 50 states and the District of Columbia allow licensed certified Physician Assistants (PAs) prescription authority (with some states, limitations exist to controlled substances). All 50 states allow registered certified nurse practitioners and other advanced practice registered nurses (such as certified nurse-midwives) prescription power (with some states including limitations to controlled substances).[11][12] Many other healthcare professions also have prescriptive authority related to their area of practice. Veterinarians and dentists have prescribing power in all 50 states and the District of Columbia. Clinical pharmacists are allowed to prescribe in some states through the use of a drug formulary or collaboration agreements. Florida pharmacists can write prescriptions for a limited set of drugs.[13] In all states, optometrists prescribe medications to treat certain eye diseases, and also issue spectacle and contact lens prescriptions for corrective eyewear.[14] Several states have passed RxP legislation, allowing clinical psychologists (PhDs or PsyDs) who are registered as medical psychologists and have also undergone specialized training in script-writing to prescribe drugs to treat emotional and mental disorders. Chiropractors may have the ability to write a prescription, depending on scope of practice laws in a jurisdiction.

In August 2013, legislative changes in the UK allowed physiotherapists and podiatrists to have independent prescribing rights for licensed medicines that are used to treat conditions within their own area of expertise and competence.[15]

Legibility

Prescriptions, when handwritten, are notorious for being often illegible. In the US, illegible handwriting is at least indirectly responsible for the deaths of 7,000 people annually, according to a July 2006 report from the National Academies of Science's Institute of Medicine (IOM). Historically, physicians used Latin words and abbreviations to convey the entire prescription to the pharmacist. Today, many of the abbreviations are still widely used and must be understood to interpret prescriptions. At other times, even though some of the individual letters are illegible, the position of the legible letters and length of the word is sufficient to distinguish the medication based on the knowledge of the pharmacist. When in doubt, pharmacists call the medical practitioner. Some jurisdictions have legislated legible prescriptions (e.g. Florida).[16] Some have advocated the elimination of handwritten prescriptions altogether[17] and computer printed prescriptions are becoming increasingly common in some places.

Conventions for avoiding ambiguity

Over the years, prescribers have developed many conventions for prescription-writing, with the goal of avoiding ambiguities or misinterpretation.[18][19][20] These include:

  • Careful use of decimal points to avoid ambiguity:
    • Avoiding unnecessary decimal points: a prescription will be written as 5 mL instead of 5.0 mL to avoid possible misinterpretation of 5.0 as 50.
    • Always using zero prefix decimals: e.g. 0.5 instead of .5 to avoid misinterpretation of .5 as 5.
    • Avoiding trailing zeros on decimals: e.g. 0.5 instead of .50 or 0.50 to avoid misinterpretation of .50 as 50.
  • "mL" is used instead of "cc" or "cm3" even though they are technically equivalent to avoid misinterpretation of 'c' as '0' or the common medical abbreviation for "with" (the Latin "cum"), which is written as a 'c' with a bar above the letter. Further, cc could be misinterpreted as "c.c.", which is a rarely used abbreviation for "take with meals" (the Latin "cum cibo").
  • Directions written out in full in English (although some common Latin abbreviations are listed below).
  • Quantities given directly or implied by the frequency and duration of the directions.
  • Where the directions are "as needed", the quantity should always be specified.
  • Where possible, usage directions should specify times (7 am, 3 pm, 11 pm) rather than simply frequency (three times a day) and especially relationship to meals for orally consumed medication.
  • The use of permanent ink.
  • Avoiding units such as "teaspoons" or "tablespoons".
  • Writing out numbers as words and numerals ("dispense #30 (thirty)") as in a bank draft or cheque.
  • The use of apothecary/avoirdupois units and symbols of measure – pints (O), ounces (), drams (), scruples (), grains (gr), and minims () – is discouraged given the potential for confusion. For example, the abbreviation for a grain ("gr") can be confused with the gram, abbreviated g, and the symbol for minims (♏), which looks almost identical to an 'm', can be confused with micrograms or metres. Also, the symbols for ounce (℥) and dram (ℨ) can easily be confused with the numeral '3', and the symbol for pint (O) can be easily read as a '0'. Given the potential for errors, metric equivalents should always be used.
  • The degree symbol (°), which is commonly used as an abbreviation for hours (e.g., "q 2-4°" for every 2–4 hours), should not be used, since it can be confused with a '0' (zero). Further, the use of the degree symbol for primary, secondary, and tertiary (1°, 2°, and 3°) is discouraged, since the former could be confused with quantities (i.e. 10, 20 and 30, respectively).

Abbreviations

Many abbreviations are derived from Latin phrases. Hospital pharmacies have more abbreviations, some specific to the hospital. Different jurisdictions follow different conventions on what is abbreviated or not. Prescriptions that do not follow area conventions may be flagged as possible forgeries.

Some abbreviations that are ambiguous, or that in their written form might be confused with something else, are not recommended and should be avoided. These are included in a separate list in Appendix 1. However, all abbreviations carry an increased risk for confusion and misinterpretation and should be used cautiously.

In continental Europe

An example prescription from 1907.

In continental Europe, prescriptions differ from their counterparts in the English-speaking world. With the exception of patient directions, they are written out entirely in abbreviations deriving from the Latin language. Furthermore, a larger proportion of prescriptions are compounded, and appropriate abbreviations and phrases exist for this. Many medical schools require up to two years of Latin as part of the curriculum for medical doctors and pharmacists.

Parts of a European prescription

A continental European prescription consists of three parts:

  • the praescriptio is the prescription itself; that is, directions to the dispensing pharmacist to supply medication, made up of the following:
    • the invocatio, consisting of the abbreviation Rp; this is analogous to the Rx used in the English-speaking world, and stands for recipe, Latin for take [from the shelf]; and
    • the ordinatio, also known as the compositio, which consists either of the brand name, strength, and number and type of dosage units of a particular drug, or else of directions written entirely in the Latin accusative case, with the exception of ingredient names, written in the genitive case. Masses are written in grammes, without the unit name. The compositio is followed by
    • the subscriptio, which consists of the directions according to which the medicament is to be prepared. An important part of this is the signatura, which is directed towards the patient and explains how to use the medication. Unlike the rest of the prescription, the signatura is written in the national vernacular.

Examples

Prescription Reading Translation
For off-the-shelf morphine tablets:
Rp.
Sevredol tbl. 60x20 mg
Exp. orig. No II (duas)
D.S. For pain 4x1 by mouth
Recipe
Sevredol tabulettae sexaginties milligrammae viginti
Expeditiones originales numero duas
Da Signa: For pain, one pill four times a day by mouth
Take
Sevredol, sixty twenty-milligramme tablets
Two packages
Directions for use: For pain, one pill four times a day by mouth
Individually compounded medication
Rp.
Pentobarbitali natrici 3
Morphiae sulphas 2
Chlorali hydrati 15
Saccharum ad 50
M.f.plv.
Div. in doses aeq. No XXX (triginta)
D.S. For sleep: one sachet to be taken at bedtime
Recipe
Pentobarbitali natrici grammata tres
Morphiae sulphas grammata duo
Chlorali hydrati grammata quindecim
Saccharum ad grammata quinquaginta
Misce fiat pulvis
Divide in doses aequales numero triginta
Da Signa: For sleep: one sachet to be taken at bedtime
Take
of pentobarbitone sodium, three grammes
of sulphate of morphia, two grammes
of hydrate of chloral, fifteen grammes
of table sugar, enough to make fifty grammes
Mix to make powder
Divide into thirty equal doses
Directions for use: For sleep: one sachet to be taken at bedtime

Other conventions

Should a patient require a dosage in excess of the maximum as established by the appropriate governmental body, this is marked by an exclamation mark and the highest recommended dosage in Latin. If this is not done, it is the responsibility of the pharmacist to contact the doctor as to dose requirements, or amend the dose to the highest recommended one.

In emergency situations, a prescription pad may not be available. In this situation, any piece of paper will do, provided it is marked Periculum in mora!; that is, danger in delay (other designations, such as Cito! or Statim!, are also used and understood). Such ad-hoc prescriptions have a limited period of validity; typically, this is the day after the prescription is written.

A doctor may self-prescribe, or prescribe for their family; this is done by replacing the signatura by the Latin phrase pro manus medici (for medical hands) or ad usum proprium (for own use). This is to be done with caution; certain drugs self-prescribed will arouse suspicion, and may result in investigation by the medical board or another governmental body.

Brand-name drugs may be swapped for generics; if this is not wanted by the doctor, they may write dispense as written in the local language on the prescription.

Non-prescription drug prescriptions

Prescriptions are also used for things that are not strictly regulated as a prescription drug. Prescribers will often give non-prescription drugs out as prescriptions because drug benefit plans may reimburse the patient only if the over-the-counter medication is taken under the direction of a medical practitioner. Conversely, if a medication is available over-the-counter, prescribers may ask patients if they want it as a prescription or purchase it themselves. Pharmacists may or may not be able to price the medication competitively with over-the-counter equivalents. If the patient wants the medication not under prescription, the prescriber is usually careful to give the medication name to the patient on a blank piece of paper to avoid any confusion with a prescription. This is applied to non-medications as well. For example, crutches, and registered massage therapy may be reimbursed under some health plans, but only if given out by a prescriber as a prescription. Some software now requires a prescription.[21]

Prescribers will often use blank prescriptions as general letterhead. Legislation may define certain equipment as "prescription devices".[22] Such prescription devices can only be used under the supervision of authorized personnel and such authorization is typically documented using a prescription. Examples of prescription devices include dental cement (for affixing braces to tooth surfaces), various prostheses, gut sutures, sickle cell tests, cervical cap and ultrasound monitor.

In some jurisdictions, hypodermic syringes are in a special class of their own, regulated as illicit drug use accessories[23] separate from regular medical legislation. Such legislation will often specify a prescription as the means by which one may legally possess syringes.

Prescription may also be used as a short form for prescription drugs to distinguish from over-the-counter drugs. In reference to the entire system of controlling drug distribution (as opposed to illicit drugs), "prescription" is often used as a metaphor for healthy directions from a prescribing medical practitioner. A green prescription is direction from a medical practitioner to a patient for exercise and healthy diet.

History

The idea of prescriptions dates back to the beginning of history. So long as there were medications and a writing system to capture directions for preparation and usage, there were prescriptions.[24]

Modern prescriptions are actually extemporaneous prescriptions (from the Latin ex tempore = at/from the time),[25] meaning that the prescription is written on the spot for a specific patient with a specific ailment. This is distinguished from a non-extemporaneous prescription that is a generic recipe for a general ailment. Modern prescriptions evolved with the separation of the role of the pharmacists from that of the physician.[26] Today the term extemporaneous prescriptions is reserved for compound prescriptions that requires the pharmacist to mix or compound the medication in the pharmacy for the specific needs of the patient.

Predating modern legal definitions of a prescription, a prescription traditionally is composed of four parts: a superscription, inscription, subscription, and signature.[27]

The superscription section contains the date of the prescription and patient information (name, address, age, etc.). The symbol "℞" separates the superscription from the inscriptions sections. In this arrangement of the prescription, the "℞" is a symbol for recipe or literally the imperative "take!" This is an exhortation to the pharmacist by the medical practitioner, "I want the patient to have the following medication"[28] – in other words, "take the following components and compound this medication for the patient."

The inscription section defines what is the medication. The inscription section is further composed of one or more of:[29]

  • a basis or chief ingredient indended to cure (curare)
  • an adjuvant to assist its action and make it cure quickly (cito)
  • a corrective to prevent or lessen any undesirable effect (tuto)
  • a vehicle or excipient to make it suitable for administration and pleasant to the patient (jucunde)

The subscription section contains dispensing directions to the pharmacist. This may be compounding instructions or quantities.

The signature section contains directions to the patient[30] and is often abbreviated "Sig."[31] or "Signa."[32] It also obviously contains the signature of the prescribing medical practitioner though the word signature has two distinct meanings here and the abbreviations are sometimes used to avoid confusion.

Thus sample prescriptions in modern textbooks are often presented as:

℞:  medication
Disp.:  dispensing instructions
Sig.: patient instructions

Use of technology

As a prescription is nothing more than information among a prescriber, pharmacist and patient, information technology can be applied to it. Existing information technology is adequate to print out prescriptions. Medical information systems in some hospitals do away with prescriptions within the hospital. There are proposals to securely transmit the prescription from the prescriber to the pharmacist using smartcard or the internet.[33] In the United Kingdom a project called the Electronic Transfer of Prescriptions (ETP) within the National Programme for IT (NPfIT) is currently piloting such a scheme between prescribers and pharmacies.

Within computerized pharmacies, the information on paper prescriptions is recorded into a database. Afterwards, the paper prescription is archived for storage and legal reasons.

A pharmacy chain is often linked together through corporate headquarters with computer networking. Walgreens, for example, uses satellite technology to share patient information. A person who has a prescription filled at one branch can get a refill of that prescription at any other store in the chain, as well as have their information available for new prescriptions at any branch.

Some online pharmacies also offer services to customers over the internet. Walgreens' web site, for example, allows customers to order refills for medicine over the internet, and allows them to specify the store that they will pick up the medicine from. Their web site also allows consumers to look up their prescription history, and to print it out.

Many pharmacies now offer services to ship prescription refills right to the patient's home. CVS, for example, will ship refills free of charge. They also offer mail service where you can mail in a new, original prescription and a signed document, and they will ship the filled prescription back to you.

Pharmacy information systems are a potential source of valuable information for pharmaceutical companies as it contains information about the prescriber's prescribing habits. Prescription data mining of such data is a developing, specialized field.[34]

Many prescribers lack the digitized information systems that reduce prescribing errors.[35] To reduce these errors, some investigators have developed modified prescription forms that prompt the prescriber to provide all the desired elements of a good prescription. The modified forms also contain pre-defined choices such as common quantities, units and frequencies that the prescriber may circle rather than write out. Such forms are thought to reduce errors, especially omission and handwriting errors and are actively under evaluation. (See: Kennedy AG, Littenberg B. A Modified Outpatient Prescription Form to Reduce Prescription Errors. Joint Commission Journal of Quality and Safety 2004; 30:480-487.)

See also

Notes

  1. Belknap 2008.
  2. "Guide to Good Prescribing - A Practical Manual: Part 3: Treating your patients: Chapter 9. STEP 4: Write a prescription". apps.who.int. Retrieved 26 March 2018.
  3. "Recipe definition". M-w.com. 2007-04-25. Retrieved 2014-01-02.
  4. Oxford English Dictionary, articles on the letter "R" (sense 14b) and the word "recipe."
  5. Eye of Horus, Eye of Ra (Udjat, Wedjat) Archived October 12, 2007, at the Wayback Machine.
  6. "First recorded incidence of the pharmaceutical sign 'Rx'". Egyptphoto.ncf.ca. Retrieved 2012-02-13.
  7. Amy Beth Dukoff. "Did You Know Where Rx Came From?". Endomail.com. Archived from the original on 2013-10-03. Retrieved 2014-01-02.
  8. "State Laws or Statutes Governing Generic Substitution by Pharmacists". : Epilepsy.com/Professionals. 2007-04-25. Retrieved 2014-01-02.
  9. Davis, T (August 30, 2005). "Prescription Writing and the PDR". Comprehensive Care Clinic. Retrieved 2014-01-02.
  10. "US Nurse Practitioner Prescribing Law: A State-by-State Summary". Medscape. December 14, 2009.
  11. Batey MV, Holland JM (March 1985). "Prescribing practices among nurse practitioners in adult and family health" (PDF). American Journal of Public Health. 75 (3): 258–62. doi:10.2105/AJPH.75.3.258. PMC 1646172. PMID 3976950. Retrieved 2010-01-22.
  12. "Florida's Pharmacists Can Write Prescriptions". The New York Times. May 2, 1986. Retrieved 2014-01-02.
  13. "Features, November 2000". archive.org. 23 December 2001. Retrieved 26 March 2018.
  14. "Physiotherapists and podiatrists join ranks of independent prescribers". The Pharmaceutical journal. 291: 174. 20 August 2013. doi:10.1211/PJ.2013.11124528.
  15. "456.42 Written prescriptions for medicinal drugs". Florida Statutes.
  16. "Eliminate Handwritten Prescriptions Within 3 Years". Institute for Safe Medication Practices. 1999-12-07. Retrieved 2010-01-22.
  17. "Good prescription practice". archive.org. 9 July 2000. Retrieved 26 March 2018.
  18. Teichman PG, Caffee AE (2002). "Prescription writing to maximize patient safety" (PDF). Family Practice Management. 9 (7): 27–30. PMID 12221761. Retrieved 2010-01-22.
  19. Ferdman, Roberto A. "The world's first prescription-only smartphone app". Quartz (publication). Atlantic Media. Retrieved 6 January 2014.
  20. "CFR – Code of Federal Regulations Title 21". U.S. Food and Drug Administration (FDA). 2009-04-01. Retrieved 2014-01-02.
  21. "(720 ILCS 635/) Hypodermic Syringes and Needles Act". Illinois Compiled Statutes.
  22. "Pharmacy in Ancient Babylonia". History of Pharmacy. Washington State University College of Pharmacy. Archived from the original on August 18, 2009. Retrieved 2010-01-22.
  23. "Extemporaneous definition". M-w.com. 2007-04-25. Retrieved 2014-01-02.
  24. Anderson, Stuart (26 March 2018). "Making Medicines: A Brief History of Pharmacy and Pharmaceuticals". Pharmaceutical Press. Retrieved 26 March 2018 via Google Books.
  25. Potter, Samuel O.L. (1902). "Prescription Writing". A Compend of Materia Medica, Therapeutics, and Prescription Writing (sixth ed.). P. BLAKISTON'S SON.
  26. "Wayback Machine" (PDF). archive.org. 2 June 2004. Retrieved 26 March 2018.
  27. "Therapeutics". LoveToKnow Free Online Encyclopedia. 2006-02-15. Retrieved 2010-01-22.
  28. "Signature definition". M-w.com. 2007-04-25. Retrieved 2014-01-02.
  29. Archived August 26, 2003, at the Wayback Machine.
  30. Ansel, H. Pharmaceutical Calculations. 13th edition, Philadelphia. Lippincott, Williams, and Wilkins. 2010. p59-60.
  31. "IEEE Computer Society Conference Publishing Services".
  32. Zoutman DE, Ford BD, Bassili AR; Ford; Bassili (October 2000). "A call for the regulation of prescription data mining". Canadian Medical Association Journal. 163 (9): 1146–8. PMC 80247. PMID 11079059. Retrieved 2010-01-22.
  33. Zwarenstein 2007

References

  • Belknap SM, Moore H, Lanzotti SA, Yarnold PR, Getz M, Deitrick DL, Peterson A, Akeson J, Maurer T, Soltysik RC, Storm GA, Brooks I; Moore; Lanzotti; Yarnold; Getz; Deitrick; Peterson; Akeson; Maurer; Soltysik; Storm; Brooks (September 2008). "Application of software design principles and debugging methods to an analgesia prescription reduces risk of severe injury from medical use of opioids". Clinical Pharmacology & Therapeutics. 84 (3): 385–92. doi:10.1038/clpt.2008.24. PMID 18388884.
  • Bennett, Reginald Robert (1906), Medical and Pharmaceutical Latin for Students of Pharmacy and Medicine, J. & A. Churchill. Public domain; free ebook at Google Books. Subtitle: A Guide to the Grammatical Construction and Translation of Physicians' Prescriptions, Including Extensive Vocabularies and an Appendix Upon Foreign Prescriptions.
  • Zwarenstein MF, Dainty KN, Quan S, Kiss A, Adhikari NK; Dainty; Quan; Kiss; Adhikari (October 2007). "A cluster randomized trial evaluating electronic prescribing in an ambulatory care setting". Trials. 8 (1): 28. doi:10.1186/1745-6215-8-28. PMC 2092426. PMID 17915028. Retrieved 2010-01-22.
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