How to search the medical literature on the net


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How to search the best available evidence in the medical literature in less than 2 minutes.

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  • Dismayed: يفزع
  • David Sackett, the “father” of evidence-based medicine (EBM) stated that EBM is:“the conscientious and judicious use of current best evidence from clinical care research in the management of individual patients” .
  • Interventional or experimental studyIs when the investigator tests whether modifying or changing something about the study participants alters the development or course of the outcome.Observational studies Involve the investigator collecting data on factors (exposures) associated with the occurrence or progression of the outcome of interest,without attempting to alter the exposure status of participants.The investigator does not intervene or manipulate the situation in any way, he or she simply observes.
  • Hemophagocytic syndrome:Can masquerade as cirrhosis with ascites.These patients have fever, jaundice, and hepatosplenomegaly, usually in the setting of lymphoma or leukemia.Reference: de Kerguenec C, Hillaire S, Molinie V, Gardin C, Degott C, Erlinger S, Valla D. Hepatic manifestations of hemophagocytic syndrome: a study of 30 cases. Am J Gastroenterol 2001;96:852– 857.
  • Pearls: لؤلؤةThe quality of most published information is very poor: Most published information is irrelevant and/or the methods are not good. Finding the high-quality evidence is like trying to sip pure water from a hose pumping dirty water, or looking for ‘rare pearls’.
  • (1/3 of medical litterature)
  • The logrank test The most popular method of comparing the survival of groups, which takes the whole follow up period into account.The logrank test is used to test the null hypothesis that there is no difference between the populations in the probability of an event (here a death) at any time point.The analysis is based on the times of events (here recurrence ulcer bleeding deaths).If a survival time is censored, that individual is considered to be at risk of dying in the month of the censoring but not in subsequent weeks. This way of handling censored observations is the same as for the Kaplan-Meier survival curve.Because the logrank test is purely a test of significance it cannot provide an estimate of the size of the difference between the groups or a confidence interval. For these we must make some assumptions about the data. Common methods use the hazard ratio, including the Cox proportional hazards model, which we shall describe in a future Statistics Note.
  • MeSH:The National Library of Medicine’s controlled vocabulary used for indexing articles for MEDLINE/PubMed. MeSH terminology provides a consistent way to retrieve information that may use different terminologies for the same concepts.
  • How to search the medical literature on the net

    1. 1. How to search the medical literature on the net Samir Haffar M.D. Associate Professor of Gastroenterology
    2. 2. My students are dismayed when I say to them “Half of what you are taught as medical students will in 10 years have been shown to be wrong. And the trouble is, none of your teachers knows which half.” Dr Sydney Burwell Dean of Harvard Medical School
    3. 3. The Term “Evidence-Based Medicine” The term EBM was first used by David Sackett & his collegues at McMaster University in Ontario, Canada in the early 1990s. Father of EBM
    4. 4. Glasziou P, Del Mar C & Salisbury J. Evidence based medicine Workbook. BMJ Publishing Group – First edition – London – 2003. Clinical epidemiology Evidence-based medicine Evidence-based practice
    5. 5. The 3 components of EBP “EBM is the integration of best research evidence with clinical expertise & patient values” - David Sackett EBM Patient values Clinical Expertise Best research evidence
    6. 6. What is the best evidence? • The best evidence is the evidence most likely to provide an unbiased view of the truth • Bias is difference between study results & truth • Of course, we can never know the truth, but we can try to come as close as possible by performing & using well-designed & well executed studies
    7. 7. Observational Study types Interventional or experimental RCTCohort study Case-control study Cross-sectional study Case series & case report
    8. 8. Trial designs • Systematic review • Meta-analysis • Randomized clinical trial • Cohort study • Case control study • Cross-sectional study • Case series & case report Primary research Secondary research
    9. 9. Hierarchy of evidence in quantitative studies McGovern D, Summerskill W, Valori R, Levi M. Key topics in EBM. BIOS Scientific Publishers, 1st Edition, Oxford, 2001.
    10. 10. Level of evidence Ia II III IV V Oxford Centre of EBM Levels of evidence Ib Bias Bias Bias Bias Bias Bias Validity/StrengthofInference
    11. 11. 1- Ask 2- Acquire 4- Apply 5- Assess Patient dilemma Principles of EBP Evidence alone does not decide – combine with other knowledge & values 3- Appraise Hierarchy of evidence 5 A
    12. 12. Background & foreground questions Evolution of questions we ask as we progress from novices posing background questions to experts posing foreground questions Guyatt G, et al. User‟s guide to the medical literature. Essentials of evidence based clinical practice. Mc Graw Hill, 2nd ed, 2008.
    13. 13. Background questions • Sometimes Involve a single fact such as: “What is the causative agent of Chagas disease?” “What is the hemophagocytic syndrome? ” • Often Involve much more information such as: “How do I insert a jugular venous central line?”
    14. 14. Hemophagocytic syndrome • Can masquerade as cirrhosis with ascites • These patients have Fever Jaundice Hepatosplenomegaly • Usually in setting of lymphoma or leukemia de Kerguenec C et al. Am J Gastroenterol 2001 ; 96 : 852 – 857.
    15. 15. Searching background questions Easy to search • Standard textbooks such as Harrison, Nelson…. • Innovative electronic texts such as UpToDate • Some companies group collections of textbooks MDConsult Stat!Ref http:// • Entry of single concept such as disease or diagnostic test
    16. 16. Textbooks Textbooks may be a useful source of information on “background” questions but: • May provide biased advice • Rapidly become out of date
    17. 17. • Questions that provide the evidentiary basis for specific clinical decisions • Best structured using the framework of: - Patient - Intervention - Comparison (if relevant) - Outcomes Foreground questions PICO/PIO
    18. 18. P I C O Patient Patient or Problem in question Intervention Intervention, test, or interest exposure Comparaison Comparison interventions (if relevant) Outcome Outcome(s) of interest Formulating a foreground question Good question should have 3 or 4 components Concept of PICO/PIO
    19. 19. Example of PICO/PIO Concept • 70-year-old man with PUD & stable angina tt by low- dose aspirin, statin, ACE inhibitor & nitrates as needed • The patient developed recently an UGI bleeding UGI endoscopy revealed no ulcer & biopsy was – for HP • You wonder if clopidogrel is more effective than the association of PPI & asipirin for recurrent PU bleeding
    20. 20. Key components of your clinical question PICO P I C O Patient Elderly patient with aspirin-associated PU Intervention Clopidogrel Comparaison PPI + Aspirin Outcome Recurrent PU bleeding
    21. 21. Formulation of the relevant question In a elderly patient with aspirin-associated PU, is clopidogrel more effective than PPI & aspirin to prevent recurrence of PU bleeding?
    22. 22. Medical literature • Published 22 000 biomedical journals ≈ 5 000 journals indexed in Medline 17 000 biomedical books annually • Gray literature Conference proceedings Reports Theses Unpublished studies Glasziou P et al. Systematic reviews in health Care – A practical guide. Cambridge University Press, Cambridge, 1st edition, 2001
    23. 23. The amount of medical literature 0 500000 1000000 1500000 2000000 2500000 Biomedical MEDLINE Trials Diagnostic MedicalArticlesperYear 5,000 per day 1,500 per day 95 per day 55 per day Glasziou P, Del Mar C. Evidence based practice workbook. Blackwell Publishing, 2nd edition, 2007. So much evidence, so little time
    24. 24. How can I find what I am searching for?
    25. 25. 50,000 articles/yr from 120 journals ~3,000 articles/yr meet critical appraisal & content criteria (94% noise reduction) McMaster PLUS project – First level Critical appraisal filters  Valid  Ready for clinical attention Health Information Research Unit – McMaster University – Canada
    26. 26. ~3,000 articles/yr meet critical appraisal & content criteria (95% noise reduction) McMaster PLUS Project Clinical Relevancy Filter (MORE)* ~5-50 articles/yr for authors of evidence- based clinical topic reviews ~25 articles/yr for clinicians (99.95% noise reduction) * MORE McMaster Online Rating of Evidence
    27. 27. High quality/relevant data – Pearls Glasziou P, Del Mar C. Evidence based practice workbook. Blackwell Publishing, 2nd edition, 2007. Finding high-quality evidence like searching for „rare pearls‟
    28. 28. High quality/relevant data Pearls If not valid No value If not relevant No value
    29. 29. Availability Most efficient resources are expensive • Academic physicians Free access of their medical school or hospital libraries • Physicians in private practice in reach countries Free access to some resources by professional associations • Health professionals in developing countries Institutional access through the WHO HINARI 1 project Free access to developing countries (BMJ PG 2 – NEJM ..) 1 HINARI*: Health InterNetwork Access to Research Initiative 2 BMJ PG: British Medical Journal Publishing Group
    30. 30. Free medical resources on the net • PubMed Central • Certain journals CMAJ – BMJ Most BioMed Central journals: • Merck Manual: • Free Medical Journals:
    31. 31. PubMed Central
    32. 32. PubMed Central
    33. 33. PubMed Central (A – B)
    34. 34. • Very popular with generalists, specialists, & house staff – Ease of use – Comprehensiveness – Inclusion of disease-oriented formation • Provides recommendations (guidelines) for clinicians
    35. 35. Synthesis < 50 000 • Systematic review of articles • Clinical practice guidelines • You assess the information & make decisions
    36. 36. Synthesis Category Comprehensiveness Easy to use Cost nearest $50 late 2007 CDSR1 Therapy & prevention Easy $300 whole library Free abstracts Clinical practice guidelines2 US & other nations Compare guidelines Easy Free Many free full-text UK national library for health Easy Ontario Medical Association Collection of preappraised guidelines Easy Free summaries Many free full-text 1 CDSR: Cochrane Database of Systematic Reviews 2 Clinical practice guidelines: US National Guidelines Clearinghouse database
    37. 37. Synthesis Category Website Systematic Reviews CDSR1 Guidelines: Clinical practice guidelines2 UK National Library for Health Ontario Medical Association 1 CDSR: Cochrane Database of Systematic Reviews 2 Clinical practice guidelines: US National Guidelines Clearinghouse database
    38. 38. Cochrane collaboration Database available free online in many countries
    39. 39. Smith G. D. et al. BMJ 1998 ; 316 : 221 - 225 Pioneer in health services research His visions are at the heart of Cochrane Collaboration Archie Cochrane (1909 – 1988) British physician & epidemiologist
    40. 40. In a 1979 article* ‘It is surely a great criticism of our profession that we have not organized a critical summary, by specialty or subspecialty, adapted periodically, of all relevant RCT’ ** Cochrane AL (1979). 1931–1971: A critical review, with particular reference to medical profession. In: Medicines for Year 2000, Office of health economics, London. Archie Cochrane
    41. 41. Corticosteroids for preterm birth • 1972 RCT showing improved outcomes for preterm babies when mothers were given short course of corticosteroid before birth • 1972- 89 6 RCTs published confirmed 1972 findings • 1989 First published meta-analysis • 1989-91 Seven more studies reported Corticosteroid reduces odds of babies dying from immaturity by 30 – 50% but thousands of babies died or suffered unnecessarily since 1972 because doctors did not know about effectiveness of tt
    42. 42. Cochrane collaboration Database available free online in many countries
    43. 43. The Cochrane collaboration Established in september 1992 in Oxford • Cochrane reviews provide substantial amount of evidence in health care & widely cited in guidelines • > 6000 people in > 100 countries working for Cochrane • 25 further centers all over the world • Much of this work unpaid but vital financial support has come from governments & other funders
    44. 44. Cochrane centers & branches 25 centers & branches
    45. 45. The Cochrane library • CDSR (Cochrane Database of Systematic Reviews) 13 385 reviews as of the 2008, Issue 1 1 786 posted protocols of reviews in progress • CCTR (Cochrane Controlled Trials Register) Largest electronic compilation of CT in existence 527 885 citations as of the 2008, Issue 1 • DARE (Database of Reviews of Effects) Free abstracts – Thousands
    46. 46. The Cocrhane collaboration
    47. 47. Primary Studies Millions • Original or primary studies eg, those stored in MEDLINE & EMBASE • Needs evaluation before application to clinical problems
    48. 48. Finding good answers Primary studies
    49. 49. Primary studies Category Comprehensiveness Easy to use Cost nearest $50 late 2007 CCTR1 All specialties Best way to find published CT Easy to use $300 whole library Free abstracts 1 CCTR Cochrane Controlled Trials Registry 2 CINAHL Cumulative Index to Nursing & Allied Health Literature 3 EMBASE Large European database PubMed All disciplines Clinical application articles Hard to use (Large size) Free CINAHL2 Nursing database Hard to use (Large size) High cost EMBASE3 Similar to PubMed Hard to use (Large size) High cost
    50. 50. Primary studies Category Website CCTR1 PubMed CINAHL2 EMBASE3 1 CCTR Cochrane Controlled Trials Registry 2 CINAHL Cumulative Index to Nursing & Allied Health Literature 3 EMBASE Large European database
    51. 51. US National Library of Medicine Moved to its current quarters in Bethesda on campus of NIH in 1962 Collections include > 7 million books, journals, technical reports, microfilms manuscripts, photographs & images Logo of the NLM The world's largest medical library
    52. 52. • Interface to MEDLINE (NLM*) & easiest way to use it • From 1950 to date • 19 million articles as of November 2009 • Growing at rate of 700 000 articles/year • ≈ 5 000 indexed journals • > 70 million search done each month • Search terms by topics, authors or journal Free on the Internet since the mid-1990s * US NLM: United States National Library of Medicine
    53. 53. Annual addition of articles to PubMed 50 years ago Majority of research not published in English Currently Almost 90% of articles published in English
    54. 54. PubMed tutorial • Side bar of the PubMed entry page • Quite detailed tutorial program • Takes about 2 hours to go right through • Very helpful
    55. 55. PubMed Tutorials
    56. 56. EMBASE • Large European database (> 11 million citations) • Similar to MEDLINE in scope & content • Strengths in drugs & allied health disciplines • Clinicians are unlikely to use EMBASE (high cost) • 70% of citations not included in MEDLINE
    57. 57. Medline Embase Cochrane Trials Registry Comparing Medline & Embase Overlap of 2 databases: 34% MEDLINE: better coverage of US journals EMBASE: better coverage of European journals Smith BJ et al. Med J Aust 1992 ; 157 : 603 – 11.
    58. 58. Key statistics for MEDLINE & EMBASE MEDLINE EMBASE No. of journal articles 10 million 8 million No. reference added annually 400 000 references 415 000 references No. of journals 3900 journals/40 languages 4000 journals/70 countries Specific thesaurus for indexing MeSH EMTREE English abstracts 76% of references 80% of references Date of coverage 1950 to present 1974 to present Availability Internet (free) – CD Internet (expensive) – CD Journals published in US 52% 33% English language articles 88% 90% Records on database Twice a week 15 days of journal receipt Egger M et all. Systematic reviews in health care: Meta-analysis in context. BMJ Publishing Group, London, 2nd edition, 2001.
    59. 59. Searching for primary studies • MEDLINE (US NLM*) one of most available systems PubMed interface of MEDLINE • Useful tutorial with trial & error learning • Type sentence or phrases representing what you search • Choice of terms based on PICO/PIO format * US NLM: United States National Library of Medicine
    60. 60. Key components of your clinical question PICO P I C O Patient Elderly patient with aspirin-associated PU Intervention Clopidogrel Comparaison PPI + Aspirin Outcome Recurrent PU bleeding
    61. 61. Text word & MeSH term* • Text word Any word or phrase in the title or abstract of an article • MeSH terms Vocabulary used to index all MEDLINE articles • Example: “hemorrhage” [Text Word] “haemorrhage” [Text Word] “hemorrhage” [MeSH Terms] * MeSH: Medical Subject Headings in PubMed
    62. 62. MeSH Database
    63. 63. Tree structure of MeSH in PubMed The „explode‟ (exp) feature of tree structure allows to capture entire subtree of MeSH* terms within single word One of 3 MeSH categories of peptic ulcer * MeSH: Medical Subject Headings in PubMed
    64. 64. Alternative spellings & misspellings (a) hemorrhage American spelling [Mesh term] (b) haemorrhage British spelling (c) hemorhage Misspelling (d) haemorhage Misspelling
    65. 65. Boolean operator ‘OR’ After its creator George Boole Akobeng AK. Arch Dis Child 2005 ; 90 : 837 – 840.
    66. 66. Akobeng AK. Arch Dis Child 2005 ; 90 : 837 – 840. Boolean operator ‘AND’ After its creator George Boole
    67. 67. Akobeng AK. Arch Dis Child 2005 ; 90 : 837 – 840. Boolean operator ‘NOT’ After its creator George Boole
    68. 68. Boolean search After its creator George Boole Boolean operators Meaning Peptic ulcer OR Hemorrhage Peptic ulcer AND Hemorrhage Peptic ulcer NOT Hemorrhage
    69. 69. ‘Wildcards’ malig* means malignancy malignant malign but not malunion malaligned etc
    70. 70. PubMed command – 1 Command What it does? OR Finds articles containing either of specified words Ex: child OR adolescent AND Finds articles containing both specified words Ex: child AND adolescent NOT Excludes articles containing the specified word Ex: child NOT adolescent Glasziou P, Del Mar C. Evidence based practice workbook. Blackwell Publishing, 2nd edition, 2007. Limits Articles restricted in several ways by: date, language, age, … ( ) Use parentheses to group words Ex: (colorectal cancer) AND (screen AND mortality)
    71. 71. PubMed command – 2 Command What it does? * Truncation Acts as a wildcard indicating any further letters Ex: child * = (child OR childs OR children OR childhood) Glasziou P, Del Mar C. Evidence based practice workbook. Blackwell Publishing, 2nd edition, 2007. [ti] Finds articles with the word in title Ex: ulcer [ti] = find article with the word ulcer in title [so] or so Find articles from a specific source Ex: ulcer AND BMJ [so] = finds articles on ulcer in BMJ MeSH Controlled vocabulary keywords used in also in Cochrane Often useful to use both MeSH heading & text words
    72. 72. PubMed translation of query into search terms PICO Element Search terms for PubMed P Elderly patient Peptic ulcer Limit to “aged: 65+ years” “peptic ulcer” [MeSH term] I Clopidogrel “clopidogrel” [MeSH term] C PPI Aspirin “proton pump inhibitors” [MeSH term] “aspirin” [MeSH term] O Recurrence Peptic ulcer bleeding “recurrence” [MeSH term] “peptic ulcer hemorrhage” [MeSH term] Other RCT Limit to “randomized controlled trial”
    73. 73. PubMed Clinical Queries • Search faster & more relevant articles • Category Etiology, dg, therapy, prognosis, clinical prediction guides • Search Narrow specific search Broad sensitive search
    74. 74. PubMed Clinical Queries
    75. 75. PubMed Clinical Queries
    76. 76. N Engl J Med 2005 ; 352 : 238 – 44. Clopidogrel vs aspirin & esomeprazole Difference 7.9 % points 95 % CI: 3.4 – 12.4 P = 0.001 by log-rank test
    77. 77. How to improve your PubMed search? • “Related Articles” link • Select another set of terms & try again • “AbstractPlus” format • “Limits” link: sex, age, language, RCT,… • “MeSH” terms: Medical Subject Headings
    78. 78. Related articles link
    79. 79. “Limits” link
    80. 80. “Limits” link
    81. 81. Question type & study design Study DesignQuestion Intervention RCT Incidence & prognosis Cohort study Prevalence Cross-sectional study Etiology & risk factors Cohort or case-control Diagnosis Cross-sectional study In each case, SR of all available studies better than individual study
    82. 82. How many questions can doctors answer each day? 64 residents in 2 hospitals 401 consultations 280 questions (2 for 3 patients) 80 answers (29%) Sources of answers: – Textbooks (31%) – Articles (21%) – Consultants (17%) Green ML et al. Am J Med 2000;109:218–233. Residents 103 GPs Questions collected over 2.5 d 1101 questions 702 answers (64%) Sources of answers: – Available print – Human resources – Literature search: 2 answers Ely JW et al. BMJ 1999;319: 358–361. GPs
    83. 83. Steps – Answerable question – Search – Appraise – Apply EBM & Systematic Review Find a systematic review Steps – Answerable question – Search ++++ – Appraise x 2 – Synthesize – Apply Time: 6 months – Team 2 000 articles This patient dies Systematic reviewEBM Time: 90 seconds < 20 articles This patient survives
    84. 84. Type of Question RCTs Appraisal Stop Others Diagnosis, prognosis, etiology No RCTs PubMed Clinical Queries Low quality PubMed general Other databases No Study Stop Appraisal Cohort Cross-sectional Stop SR Appraisal PubMed Clinical Queries Intervention Cochrane SR Stop Cochrane Library
    85. 85. Type of Question Intervention Others Diagnosis, prognosis, etiology Cochrane SR Stop SR Appraisal Stop RCTs Appraisal Stop No RCTs PubMed Clinical Queries Stop Appraisal Cohort Cross-sectional Low quality PubMed general Other databases No Study Cochrane Library PubMed Clinical Queries
    86. 86. Limitations of evidence • Evidence simply doesn‟t exist • Some of what is available Not easily accessible Not clinically relevant Not of good quality Not applicable to your patient It takes time to develop high quality evidence & more time to get it to publication
    87. 87. Learning through play • Try all “buttons” • Make lots of “mistakes” • Have fun
    88. 88. Mc Graw Hill 2008 References BMJ Publishing Group 2003 Elsevier 2009
    89. 89. Thank You