3007 Exam 1

• “What was learned in the first 3 years of medical school will be just 6% of what is known at the end of the decade…”. Over half the knowledge you learned will be irrelevant due to new drugs, devices, procedures, and treatment paradigms
• Book chapters (18 months old) and review articles (12 months old) may not contain contemporary data , even when newly published
• Authors might have biases or hidden agendas and you won’t know, they can manipulate the interpretation and place your patients at risk
• Authors might not divulge enough information for you to fully understand a topic
• why move past book chapters and review articles?


  your clinical specialty, book chapters or review articles disagree with each other, check primary literature for new studies that came out, formulary review on a Pharmacy and Therapeutics Committee, worried about being scammed, interested in researching this area, conducting a Drug Use Evaluation, writing your own book chapter or review article
• The formulary is the most important way a health-system assures that its clinicians has the drugs they need to care for patients without going broke in the process
• Pharmacy &Therapeutics Committee is made up of physicians, pharmacists, and the CFO; pharmacist does the review and has to present it to the entire committee, committee members can ask questions of the requestor and the pharmacist reviewer, committee votes to approve the drug for use at all and if so with or without restrictions; If you are proposing a formulary addition or doing the review and not reviewing the primary literature, someone at the meeting will eat you up
• Data scamming: over-exaggerated results, primary endpoint different, specific studies referenced without stating negatives, only positive data articles referenced s evidence
• prevent scamming: cautious when reding, test validity, meta-analysis
• Internal validity – Are these methods rigorous and can these results stand up to scrutiny
• External validity (applicability) – To what extent do these results apply to the patients I see
• meta-analysis: What is the quality of the individual studies that make up the meta-analysis and the methods the meta-analysts used? What is the strength of this body of evidence? What is the applicability of this body of evidence?
• Drug Use Evaluation (DUE): identify best practice from literature, determine drug use in establishment, find and rectify deficiencies, re-asses in future
• Skills needed for DUE: literature evaluation skills, ability to define outcomes of interest, ability to extract data from a database or set up a prospective data collection tool, and statistical analysis skills
• An in vitro study is “a type of study wherein the methodology involves a biological process made to occur outside the living organism at the laboratory for experimentation and observation”
• In vitro studies are important in explaining why effects in humans are occurring, to fill in the mechanistic rationale for seen humanistic phenomenon
• In vitro studies can provide new leads for the development of new drug molecules or new product formulations
• The use of cells in culture are, at best, a rough approximation of those that would occur in the human body; not organized like cells in organs, not oriented in position like native cells are, and are not exposed to fluctuating substrate, hormones, and tissue factor concentrations
• As cell lines age, their genetic stability can fluctuate; For example, Chinese hamster ovary cells have a predominant karyotype at baseline but after six months in culture express increasing numbers of karyotype variants while human embryonic kidney cells express chromosomal instability over time with resultant heterogeneous and unstable karyotypes    
• Imposter cells: Many cell lines used to work out basic mechanisms of cell function, interaction, and drug action are not the cell lines they are purported to be due to cross-contamination/misclassification that occurred at some point in their development or propagation
• imposter cell example: The most common are the Henrietta Lacks (HeLa) cell line; 29% different
• Mycoplasma contamination has persisted in many cell cultures for decades and alters nucleic acid synthesis pathways and chromosome breakage, induces arginine depletion, and interferes with cell fusion; Up to 1/3 of cell lines are imposter cells or mycoplasma infected cells
• imposter cells may be a major contributor to the lack of reproducibility of many in vitro basic science experiments
• >70% of researchers have tried to reproduce another scientists experiments but were unable to at some point in their careers
• Title – Present main objective or main result of study
• Abstract – Summarize objectives, methods, results and give concluding sentence
• Introduction – Background info, should make a case for doing an evaluation, should state the rationale for the study as the last sentence
• Methods – Design of study, how subjects selected, who was included/excluded, what are the methods of measurement, analytical techniques, how are groups compared
• Results – When methods applied to a population and data recorded and analyzed, what happened?  Describes findings without commentary.  Look for internal validity in methods and results.
• Discussion/Conclusion – Rehash results with a critique of study. Compare with previous knowledge/studies.  Identify limitations of the study. Delineate future studies
• goal as a literature reviewer: Determine the internal validity of individual studies and the strength of evidence within a body of evidence and Determine the applicability of individual studies and the applicability of a body of evidence 
• Descriptive Studies (Case Reports/Case Series):

  Serve to record an event or observation that occurred, describe without making a comparison
• observational Studies (Case Control/Cohort Studies): Observational studies (Case control or cohort studies) utilize comparisons, but investigators are bystanders
• Controlled Trials: Researchers give one group something or take something away from one group to find out what happens in relation to another group (the control group) or groups
• Retrospective study – A study from which information from the past was used to compare
• Prospective study – A study comparing information that will be gathered in the future
• Experimental studies are only prospective, case-controls are only retrospective, cohort studies can be both
• Case Control Study: Start in the present, look at a group with and one without an outcome, then look at a potential risk factor from the past and compare the groups
• Cohort Study: exclude those who have the outcome at baseline, Start at some time point with a population, some have potential risk factor some do not, Patients are put into groups by the risk factor with subsequent follow-up to see if those with the risk factor have greater incidence of the outcome than those without the risk factor
• random error: error due to chance, larger sample size means lower magnitude for random error