We calculated Fleiss’ kappa coefficient for inter-rater reliability  of the four faculty pharmacologists using a random sample of 40 wiki assignments. This showed a kappa score of 0.97.
Standard setting for ‘Foundations of Medicine I’ summative exams is the responsibility of the FOM grading committee, which is composed of 17 faculty members (basic or clinical science). Standard setting included consideration of the consequences to learners, defining a minimally competent response, MCQ item statistical analysis (Appendix 5), and the z-score distribution of learner performance. Between 2014 – 2018, all M1 students were judged to be competent with regard to the pharmacology summative MCQs.
Between 2014 - 2018, a range of 82 - 94% of learners in each cohort rated the social pedagogy-based pharmacology curriculum either extremely or somewhat valuable in helping them meet associated learning objectives (Table 3).
[INSERT TABLE 3 HERE]
Formative and summative assessment of wiki assignments
The percentage of students judged not competent in formative small group wiki assignments ranged from 7.8% to 15.6%. The predominant reason for not passing was learners being late with their answers (Appendix 6). All learners demonstrated competence in the final, summative individual wiki assignments. One learner in 2015 failed initially, due to lack of timely submission.
We explored free text comments from the wikis to assess the extent to which leaners acquired and applied a conceptual framework for approaching pharmacology as a discipline, and the extent to which they self-assessed their developing mastery of its underlying principles using Bloom’s taxonomy with case-based wiki exercises. Illustrative quotes for selected concepts are shown; learner names have been replaced with pseudonyms.
Learners acquired a conceptual framework for approaching pharmacology as a discipline
We functionally defined a conceptual framework as, “a network of interlinked concepts where intersecting, related abstractions provide an interpretive context that facilitates comprehension, analysis, and explanation of observed phenomena.” [38-41]. Table 4 displays coding of one representative final wiki assessment submission, broken up using ellipses ‘…’; an uninterrupted version of this individual student response can be viewed in Appendix 4. In it, the learner crisscrossed all six levels of Bloom’s taxonomy and employed an array of conceptual framework elements to interpret, evaluate, and synthesize conclusions about the stated pharmacological benefits of the OTC medication, Dream Water. As noted earlier, all learners demonstrated individual competence with this summative outcome.
[INSERT TABLE 4 NEAR HERE]
We also explored the degree to which our approach reflected key principles of social pedagogy, and found that learners were (1) routinely seeking assessment and sharing information with one another; (2) identifying peer misperceptions or errors and providing gentle correction and guidance; (3) reframing what they have learned at the molecular or cellular level in a whole patient context; (4) transferring learning to their weekly primary care clinical medical student home (MeSH) sites and applying it with patients where appropriate and under supervision; (5) providing evidence-based answers by accessing, screening, analyzing, and citing the literature base; and (6) asking their own self-generated questions of one another. Additional characteristics of social pedagogy demonstrated during wiki interactions included faculty providing external guidance to foster cognitive bootstrapping, scaffolding, and flexibility in learners; and unobtrusively monitoring learner progress and interactions online. We quantified the mean prevalence of these behaviors among the 73 wiki small groups (Table 5). Collectively, these attributes that emerged support our approach as an authentic and feasible application of social pedagogy in the education of medical students in their pre-clinical years.
[INSERT TABLE 5 HERE]
Learners established a routine practice of self-directed assessment seeking, across Bloom’s cognitive taxonomy, using the case-based wiki exercises
With respect to health professions education, traditional self-assessment has been defined as a “personal, unguided reflection on performance for the purposes of generating an individually-derived summary of one’s own level of knowledge, skill, and understanding in a particular area.” . Intuitively, learners’ analyses are turned inward; they search themselves as relevant data sources to evaluate and gauge their progress towards competence. However, the validity of this form of self-assessment is often ill-founded and inferences may correspond inaccurately to external standards [42-45]. Instead, we observed externally-oriented feedback requests and invitations consistent with Eva and Regehr’s articulation of self-directed assessment seeking, “the pedagogical process of explicitly seeking external sources of information for formative and summative assessments of one’s current level of performance and practice improvement.” . These behaviors align with initial steps in the self-directed learning process and assist integration of new knowledge [46-47]. The following passages are representative exemplars of our students' self-directed assessment seeking behaviors in the wiki assignments.
Karen:- I’m wrestling with how to reconcile acetaminophen use in children versus neonates. When the question states that metabolic pathways are reduced in the neonatal period, does that mean that there are less pathways available for the infant to metabolize the drug or that the metabolic pathways occur faster in infants? I read that “the biologic half-life of acetaminophen is somewhat shorter in children and somewhat longer in neonates” (Levy G. Comparative Pharmacokinetics of Aspirin and Acetaminophen. Arch Intern Med. 1981;141(3):279–281). Mina, you mentioned that infants are unable to do glucuronidation. In that case, for infants, where the drug elimination is hindered via the lack of a metabolism pathway, wouldn’t more of the drug be shuttled into the other two acetaminophen metabolic pathways? I thought that this would also result in higher levels of the toxic NAPQI intermediate, as the enzyme responsible for detoxifying it (glutathione synthesis) will become saturated with substrate.
- [Wiki #4; Group 13]
Nasir:- Would a partial agonist that can exhibit both antagonist and agonist activity have two allosteric binding sites that regulate its function? Or would it just have one binding site and the presence or absence of a ligand determine its response (either agonist or antagonist)?
- [Wiki #8; Group 14]
Tim:- Let me know if I overanalyzed this graph. Or analyzed it incorrectly.
- [Wiki #9; Group 13]
Darrin:- I wasn’t 100% sure about our answer to question B, so I looked at our drug interaction app on my smartphone and it shows no potential drug interactions identified. If you look at other drugs, like Digoxin, that are transported by P-glycoprotein, strong warnings exist and dosing for drugs reliant on p-glycoprotein is suggested to decrease by 50%. The other thing I would look out for a decrease in the peripheral restriction of opioids and make sure blood concentrations are low.
Sena:- That's really interesting, Darrin. Nice job thinking to check our drug interaction app! I feel like these things are always more complicated than we know! Julie alluded to different processes occurring at different rates with regard to loperamide crossing the blood barrier and being pumped out. I will layer on the glucuronidation process. If this is happening rapidly, yes there will be some loperamide available to cross the BBB, but it will not be in concentrations high enough to exert an effect. Perhaps one of the faculty can weigh in on what actually happening? Are we on the right track? :)
Tim:- This situation sounds like what we were talking about in Questions 2 and 3. I did some searching and found a site where people posted about their dependence on loperamide as a CNS agent. The discussion board talks about mu receptors, p‑glycoprotein inhibitors vs taking very large doses, etc. Interesting because it's relevant to this wiki, but also interesting as an insight into the minds of people struggling with drug dependence, their awareness of the biochemistry, and OTC medications as a target of drug abuse. https://www.drugs-forum.com/forum/showthread.php?t=194669
- [Wiki #12; Group 12]
Learners identified peer misperceptions or errors and provided gentle correction and guidance
Peer correction occurs when learners, rather than instructors, point out errors or misunderstandings to one another and help to put them right. It fosters learners’ ability to critically reason and problem solve, and supports the development of soft skills including conveying specific feedback constructively and communicating observations, comments, and actions in a manner that others will attend to and comprehend. Learning how to give and receive peer correction is something that helps prepare health professions students for their future workplace. The following passages are representative exemplars of students' peer-corrections in the wiki assignments.
Chloe:- Bryan, I think you may be mistaken. As stated in the question prompt, the volume of distribution of acetaminophen is 57 L, and as stated in the teaching video, the volume of distribution of aspirin is 11 L (not 116 L). I believe you are correct in your second sentence in part however, which indicates that acetaminophen's higher volume of distribution vs aspirin indicates that acetaminophen has a greater capacity to travel beyond the plasma and into the tissues. Great job on part B.
- [Wiki #3; Group 15]
Karen:- I think you may have made an error in your calculation for Drug 2. You converted your 1g to 1000mg but in your calculations you used 1g rather than 1000mg.
Mina:- You are absolutely right Karen! No wonder I was confused by a therapeutic index (TI) of < 1. I have made the corrections.
- [Wiki #8; Group 13]
Mina:- Thank you for the thorough explanation, Evie. I was having a hard time comprehending the curve before reading your response. Now, I am going to try to take your explanation one step further…
- [Wiki #9; Group 13]
Jorge:- Just one other thing to note, Hannah, Drug W is an antagonist of H2 receptors, not an agonist. So, even if it were to affect H1 receptors, it wouldn't cause a runny nose, watery eyes and itching: those symptoms are the result of a functioning histaminergic signaling pathway. Rather, inhibiting H1 receptors could induce the nose and eyes to dry out, while also causing drowsiness (assuming Drug W can cross the blood-brain barrier).
- [Wiki #9; Group 9]
Learners reframed molecular or cellular information to a patient context
Professional practice requires health professionals to link learning from different sources and disciplines. Here students combined and contextualized various basic science ‘elements’ they encountered in one or more learning experiences in a way that was meaningful at the level of the human patient and relevant to an authentic understanding of what they had learnt. The following passages are representative exemplars of this reframing by students in the wiki assignments.
Rani:- I remember not too long-ago seeing commercials for ‘The Purple Pill’ and Tums, each accusing each other of either taking too long to work or not working long enough. Omeprazole is an irreversible antagonist to proton pumps, which inhibits a biological response and takes days for the effect to manifest fully. Tums are made of calcium carbonate and simply raise the pH of the stomach, quickly mitigating the irritation resulting from stomach acid, but not for very long. I wonder if it would be safe to have a patient take Tums while waiting for omeprazole to kick in? They would probably need an easy-to-digest diet (which might help the heartburn in the first place), but would they be at increased risk for GI infection because the pH of the stomach might not be low enough to kill bacteria?
- [Wiki #9; Group 17]
Lily:- To link back to my question on patient compliance, I think it is interesting to consider the of patient that would be using a drug like BenGay. This patient would probably be inclined to use a heat pad due to the nature of their symptoms. Certain behaviors that cause adverse effects, such as consuming a certain medication with alcohol, seem less likely to occur together. For example, it seems unlikely that a patient who is sick in bed would also be consuming alcohol. Avoiding alcohol while sick is also fairly common sense. Patients taking medication like BenGay may unknowingly fail to comply just because they are doing what seems innocuous and common to treat their symptoms.
- [Wiki #10; Group 16]
Elias:- I thought that Darrin gave great answers. Going along with part a, I was reading about opioid overdose in an article published in the NEJM. It stated that respiratory depression (of 12 breaths or less a minute in a not sleeping patient) was one of the best signs of overdose, especially if it is coupled with constricted pupils or stupor. Darrin’s answer about the lethargy/sedation made me think of this. Here is the article if you want to read it. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3739053/
- [Wiki #12; Group 12]
Learners applied their learning at weekly primary care clinical sites (MeSH)
The pre-clerkship phase of the FHN SOM curriculum consists of three courses: Foundations of Medicine (FOM), Clinical Arts and Sciences (CAS), and Scholarly Reflection and Concentration Capstone (SRCC). CAS includes extensive small group experiential learning with standardized patients, video review, goal setting, and clinician preceptor feedback. In addition, each first- and second-year medical student is paired with a practicing community physician, and spends one day per week at either an internal medicine, pediatric, or family medicine site learning from their physician mentor (medical student home; MeSH). Under supervision, students are able to practice essential clinical skills with patients, including interviewing and examining patients, engaging in clinical reasoning skills and the diagnostic process, and assisting in creating treatment plans. The following passages are representative exemplars of how students' applied their pharmacology learning at their weekly MeSH sites in the wiki assignments.
Robyn:- I agree that dose is harder to conceptualize when the medication is a cream instead of a pill. I wonder if this would be a benefit of transdermal patches since each patch is a dose (though these are often for systemic effects not just local effects). Then again, I think the idea of a drug getting absorbed through the skin and having the desired systemic effect on the body may be hard for some patients to understand. At MeSH today, there was a patient who told me that she used nicotine patches but they didn't stick that well so sometimes she just stuck another one on. She wasn't sure if this was okay or if she was getting a double dose.
- [Wiki #10; Group 7]
Calum:- I just wanted to add to Dr. McHugh's point about addiction. Nicotine has a half-life of about 40 minutes, which explains why many people smoke a pack of cigarettes/day as it keeps their levels of nicotine relatively constant. With that said, chewing tobacco or snuff allow for easier use and therefore increase the likelihood of developing an addiction. I was able to talk about this with a patient at MeSH this week who had begun to use chewing tobacco while at work as part of his efforts to quit smoking; it was very easy for them to sit at their desks for hours with a ‘lip’. He had thought that only inhaling tobacco smoke led to nicotine addiction.
- [Wiki #13; Group 9]
Hannah:- I was discussing with my MeSH preceptor this week how to counsel a 16-year-old patient who had asked about quitting smokeless tobacco use on his baseball team. As Jacob's student physician I wanted him to quit. But I also wanted to be careful in counseling him. I was worried that, as a 16-yr-old, he might shut down and not listen, perceiving a need to be completely independent. I discussed with him the harmful effects of tobacco in all its forms, and showed him pictures of what lungs of smokers look like. We discussed him being on the baseball team and many of his teammates are chewing tobacco, so it has been hard for him to say no…I think it was important to listen to him and not just lecture him on what he should or should not be doing.
- [Wiki #13; Group 9]
Learners accessed the literature base to provide evidence-based answers
The continually expanding availability of biomedical information means that one-time knowledge learning (i.e., only while in medical school) is insufficient to deliver optimal patient care. Physicians must instead routinely gather, appraise, and interpret medical evidence in order to apply knowledge at the point of care . Here learners cited pertinent information using credible and varied evidentiary sources. The following passages are representative exemplars of how students' accessed and cited peer-reviewed literature in the wiki assignments.
Tim - I found this PubMed article on the beverage chosen during administration of aspirin. Odou P, Barthélémy C, Robert H. Influence of seven beverages on salicylate disposition in humans. J Clin Pharm Ther. 2001;26(3):187-193. http://www.ncbi.nlm.nih.gov/pubmed/11422602 It can be viewed using the library PubMed link. Some interesting factors that were brought up were...1) length of stay in stomach (due to food stuffs in orange juice slowing down stomach evacuation into the intestine; 2) solubility of aspirin in the more acidic orange juice (less soluble in strongly acidic environments, more soluble when ionized in less acidic environments). It's a catch-22 because the less soluble form of aspirin is also the more membrane permeable form that can enter the blood stream from the stomach.
- [Wiki #1; Group 8]
Luke:- I found an article from the Journal on Studies on Alcohol that related the intake of food to the enzymatic metabolism of alcohol. The authors used Michaelis-Menton Kinetics to demonstrate this fact. They also indicated that not only is the absorption of alcohol slowed, but the highest concentration of alcohol within the blood stream is lowered with an intake of food. Lastly, it takes a longer amount of time for alcohol to reach its peak concentration with food consumption. A.J. Sedman, P.K Wilkinson, E. Sakmar, D.J. Weidler, and J.G. Wagner. "Food Effects on Absorption and Metabolism of Alcohol." Journal on Studies on Alcohol 37.9 (1976): 1197-214. PubMed. Web. 14 Aug. 2014
- [Wiki #1; Group 8]
Camden:- The use of a heating pad can dramatically increase the amount of methyl salicylate absorbed through topical administration. Cooper (2007). How can you overdose on BenGay? http://scienceline.org/2007/08/ask-cooper-bengaydeath/
Andrés:- In addition to the factors mentioned by Camden, heat also causes local vasodilation and increased vascular permeability, thus higher-than-intended and faster-than-intended concentrations of the topical drug in systemic circulation. The mechanisms for this vasodilation include “the roles of temperature-sensitive afferent neurons as well as nitric oxide” (Kellogg, In vivo mechanisms of cutaneous vasodilation and vasoconstriction in humans during thermoregulatory challenges, J Appl Physiol 100: 1709 –1718, 2006).
- [Wiki #10; Group 16]
Sena:- I found an interesting article looking into whether bacteria in the gut produce GABA, and possible implications for inflammatory diseases of the bowel as well as GABAs involvement in pain signaling in the gut. American Society for Microbiology (2012). Intestinal bacteria produce neurotransmitter, could play role in inflammation. http://www.eurekalert.org/pub_releases/2012-06/asfm-ibp061312.php
- [Wiki #11; Group 12]
Evie:- I found two papers showing that nicotine increases the permeability of the Blood-Brain Barrier, which I thought was interesting. The first paper showed that more sucrose crossed the BBB with continuous administration of nicotine. The second paper reproduced that result, and also measured a decreased in MLA uptake, a selective antagonist of the nicotinic ACh receptor alpha7. This could have an impact on patients with chronic nicotine use, as they may be more affected by exposure over time. Hawkins et al. (2004). Brain Res. 2004 Nov 19;1027(1-2):48-58; Lockman et al. (2005). J Neurochem. 2005 Jul;94(1):37-44.
- [Wiki #11; Group 13]
Learners asked self-generated questions of one another
Effective teaching requires that learners not be mere receptacles of knowledge but rather they should participate meaningfully and actively in their own learning processes. One example of this is students generating questions for themselves to enhance comprehension . The following passages are representative exemplars of students’ asking self-generated questions in the wiki assignments.
Chloe:- I agree with your responses Robbie. Here are some questions of my own. Do antihistamines specifically inhibit the release of epinephrine and norepinephrine that subsequently contributes to the drowsiness effect of antihistamines? I have heard that non-drowsy antihistamines have caffeine added to them to counteract the drowsiness classically associated with antihistamines. Is this true, or are non-drowsy antihistamines formulated in such a way that they physiologically (through specific receptor binding) do not cause drowsiness?
- [Wiki #7; Group 15]
Lily:- I understand that increasing the dose would increase the concentration in a particular body compartment. In terms of lethal dosage, is this dependent on which compartment is most sensitive to the drug? For example, the concentration in one compartment could be lethal, but not in others.
- [Wiki #3; Group 16]
Mitchell:- Are there situations in adulthood where metabolic pathways are reduced as in the neonatal period? I know that some adults don't process acetaminophen (paracetamol) properly or have an adverse reaction to it, and I am wondering if the underlying mechanism could be the same as that present in a neonatal infant?
- [Wiki #4; Group 18]
Ria:- I have a question: Are Phase I enzyme polymorphisms associated with Phase II enzyme polymorphisms? Like a very rapid alcohol dehydrogenase activity polymorphism associated with a low-to-no activity acetaldehyde dehydrogenase polymorphism?
- [Wiki #5; Group 17]
Faculty provided external guidance that prompted further learning progress
Giving learners feedback to guide their progress has always been viewed as beneficial to learning; however, the need to combine opportunities for learner reflection and coaching with feedback to help learners achieve anticipated outcomes has been under-stressed . In a learner-centered coaching approach, teachers use available formative performance data to contribute specific feedback that is relevant to fostering continued momentum towards mutually discernible instructional targets. The following passages are representative exemplars of faculty providing external guidance to prompt further learning progress in the wiki assignments.
Dr. McHugh: Strong work, Ahmed. Would anyone like to comment on volume of distribution (VD) and whether we would want a drug with a high VD or a low VD administered to treat a patient with bacteremia? And why?
Rani:- Bacteremia is the presence of bacteria in the blood. To effectively combat the infection, the (presumably) antibiotic should remain at the site of infection. This means the drug should have a low VD. It won't distribute to the body compartments but instead remains in the plasma where it has the best chance of fighting the infection.
- [Wiki #3; Group 17]
Dr. Macica:- Padme, I'm glad you're thinking about the impact of blood flow (and tissue extraction rate); does anyone want to comment on how this helps inform the question about Mrs. N and the synovial joint ?
- [Wiki #3; Group 14]
Dr. Hall:- Yasin, Can you clarify a bit? C0 is a derived value. The drug distributes quickly and we can't really ‘catch’ the concentration of drug at time=0. How do we extrapolate from your sampling data to obtain C0?
Yasin:- We could use the data from the blood samplings to plot the change in dose over time. We could then use the plot to extrapolate the exact dosage at time = 0 by utilizing a curve that best fits the data. Fitting the plot to a curve does not yield the Co value- you can see from the video that the curve is extrapolate back to t=0 to obtain an estimate for C0.
- [Wiki #3; Group 4]
Dr. McHugh:- What do you folks think about the fact that we are talking about OTC drugs here, and that there will be many people taking them who really have different alleles for CYP2D6? Do you that as the availability of individual genetic testing increases in the future, people will want to know about their CYP450 profile? Or do you anticipate people will be scared of genetic profiling information?
Ria:- I think that to a certain degree there will be self-selection of how people choose to take OTC medications. I know that I have a funny reaction to diphenhydramine unless I take it under specific circumstances, and I know others who refuse to take other kinds of OTC medication because of the reactions they've had. It's very likely that these odd reactions could be based on genetic polymorphisms, but we didn't have to do genetic testing to find that out. I think people will certainly want to know their genetic profile, out of curiosity or medical concern or both. The popularity of genetic sequencing and interpretation services (e.g., 23 And Me) speaks to that desire. However, there are two downsides to gaining that knowledge: 1) Having that knowledge of the near-certainty of things that may happen to you (if there are indeed nasty surprises lurking in your DNA), and 2) health insurance companies knowing the same thing. Everything is a risk-reward analysis, and I think it should be left up to individuals to make the decision to access that knowledge.
- [Wiki #5; Group 17]
Dr. McHugh:- Are you confident that folic acid can diffuse through cell membranes at pH 6? Despite the +1 of the amino group and the -1 of the carboxylic acid canceling each other out in the overall sense, you still have a molecule that has two charged functional groups (i.e., a zwitterion). Do you folks think there is a difference between 'neutral' and 'uncharged' when it comes to crossing the plasma membrane. Module #1's teaching video outlined 4 main ways by which small molecules cross cell membranes.
- [Wiki #2; Group 14]