The Medical Decoder Spring 2017 by The Medical Decoder

IN THIS ISSUE Science & Technology 4

Superbugs on the Rise Brooke Mahoney Northwestern University '20

Genomic Sequencing: The Future of Medical Profiling Thomas Dent University of Michigan '19

Deleting Disease with CRISPR Cas-9 Troy Biermann & Srijit Paul Northwestern University '20

The Medical Experience 12

The Journey to a 523 Shannon He

Northwestern University '18

What I Wished I Asked Sarah Smith

Medical Voluntourism Eric Kim

University of Michigan School of Medicine, '20

Northwestern University '18

Health Care & Policy 19

Pharmaceutical Prices: Formulating a Cure Nathan Shlobin Northwestern University '20

Human Interest 21

Medical Error Karol Bisaga

Northwestern University '20

2 â&#x20AC;˘ The Medical Decoder â&#x20AC;˘ Spring 2017

Editors-in-Chief

Korri Hershenhouse Eric Kim

Creative Director

James Guo

Business

Matthew Lam Evan Sitar

Writing Staff

Troy Biermann Karol Bisaga Thomas Dent Shannon He Eric Kim Brooke Mahoney Srijit Paul Nathan Shlobin Sarah Smith

Editing Staff

Michael Albert Eugenie Bang Troy Biermann Regina Fricton Shannon He Uma Jacobs Monica Juarez Christina Liu

LETTER FROM THE EDITORS

Dear readers, Welcome to the ninth edition of The Medical Decoder!

Editing Staff (cont.) Srijit Paul Charlie Schwartz Rachel Seng Nathan Shlobin Aditya Tanjore Carson Wilmouth

Design Team

Mariam Ardehali Karol Bisaga Angie Chen Esther Chung Matthew Lam Charlie Schwartz Jacqueline Tang Carson Wilmouth Victoria Wu

We journey with you in this edition from preparation for medical school, through to complexities of practicing medicine, and all the way to the future intricacies of treatment as healthcare and technology evolve. The road to a medical career begins early on with the premedical experience in college. In “My Journey to an MCAT 523,” Shannon He offers advice on how to tackle one of the most daunting aspects of medical school application, the MCAT. Then, we zoom out and delve into what the future holds for the biotechnology field. In our first ever cover article featuring a writer from outside of Northwestern, Thomas Dent brings into focus the progress toward basing treatment plans around the specific genetic profile of each patient in his article “Genomic Sequencing: The Future of Medical Profiling.” Continuing on the theme of genetics-based therapeutics, Srijit Paul and Troy Biermann discuss the possible applications of an emerging gene editing tool in "Deleting Disease with CRISPR Cas-9." We are extremely proud of this issue; we endeavored to shed light on new developments in medicine and their implications for the future. Thank you to our dedicated writers, staff and readers for continuing to grow this publication. We hope this edition serves to guide you through your various steps on the journey as a contributor to the healthcare sphere. We are pleased to present the ninth edition of The Medical Decoder. Happy reading!

Sincerely, Korri Hershenhouse and Eric Kim Editors-in-Chief medicaldecoder@gmail.com

Letter from the Editors • Volume 9 • 3

Superbugs on the Rise The misuse of antibiotics strengthens resistance of bacteria By Brooke Mahoney

lmost every American has likely been on some form of antibiotic in his or her lifetime. Most have probably been given a prescription for antibiotics within the last year. When these medications are prescribed and used responsibly, they are effective and curative. However, their effectiveness, small dosage, and few side effects can cause them to be abused. When a person walks into a doctor’s office with a viral infection, asks for antibiotics, and receives a prescription even though it is not medically

necessary, it doesn’t seem like such a big deal. The antibiotics can’t be harmful, right? According to the Center for Disease Control (CDC), 266.¹ million courses of antibiotics were dispensed in pharmacies in the United States to outpatients in 2014, correlating to over five prescriptions for every six people in the country each year. What makes this even more unsettling is that at least 30% of prescribed antibiotics are completely unnecessary and about 50% of all outpatient antibiotic use is inappropriate -

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consisting of either unnecessary use or inappropriate selection, dosing, or duration of use.⁷ This misuse is one of the reasons we, as a society, have arrived at almost the same point we were at before the discovery of antibiotics. In 1942, during one of the first uses of antibiotics, a woman was cured of streptococcal sepsis by being administered the newly discovered substance of penicillin and went on to live to be 90 years old. Today, many people die from infections in hospitals

even with the administration of antibiotics, creating a fear of disease similar to that in the pre-antibiotic era.² In fact, in January of 2017, a woman from Nevada died of a superbug resistant to every antibiotic available in the United States.³ Even though antibiotics are widely available nowadays, infectious diseases are still a common cause of death worldwide and in the US. Beyond the misuse of antibiotics, the larger force at work is the extremely powerful nature of microbes. Since microbes have been on Earth for 3.5 billion years, they outnumber humans by a factor of 1022 and can cycle through 500,000 generations in the time humans go through one. Due to this rapid replication and their genetic plasticity, they have learned to adapt to different environments. Moreover, since antibiotics were not invented but actually discovered by humans, microbes have had billions of years to evolve and

adapt to resist them.⁴ Therefore, the main cause of the antibioticresistant superbugs sweeping across the world today is the ability of microbes to adapt. However, this process is accelerated by practices such as the misuse of prescription antibiotics and the excessive use of antibiotics in farming. Human activity is thus increasing the rate of the antibacterial resistance that naturally occurs in microbes, creating the rampant antibiotic resistance there is today.⁴ The problem with superbugs is the lack of treatments to combat them: the bacteria have evolved to become resistant to all antibiotics known to humans. The solution to this problem would ultimately be the continuous development of new antibiotics so that there are constantly new drugs that microbes have not had the opportunity to become resistant to.⁴ However, this ideal model is currently not in practice because

of the lack of financial resources necessary for research into antibiotic development. The main reason for this insufficient funding is that antibiotics do not produce a great return on investment due to the fact that they are relatively inexpensive and used for a short amount of time. In comparison to research on other drugs such as HIV retroviral medications, there is much less research and new drug development for antibiotics. HIV medications and other drugs that people tend to start using at a relatively young age and continue to use for the rest of their lives are produced at the most rapid rate because they produce the biggest investment return for pharmaceutical companies.⁴ In 2015, the NIH reported that there was $3 billion of funding for HIV/AIDS research while only $310 million of funding for research into antimicrobial resistance.⁵ This discrepancy in profitability

Science & Technology • Volume 9 • 5

leaves little opportunity for the development and discovery of new antibiotic drugs, causing those in the medical community to look for other solutions. Some of these less ideal, shorter-term solutions include decreasing the amount of antibiotics used in farming and making sure that physicians use prescriptions more responsibly. Doctors thus should not prescribe antibiotics for viral infections and should instead ensure the administration of the right antibiotics for the correct duration of time at the correct dose. Along these lines, a global action plan has been placed in effect to combat antimicrobial resistance. According to the World Health Organization, the objectives of this plan are to educate people about the concept of antibacterial resistance, utilize surveillance and research to improve knowledge, reduce the instance of infections, use antibiotics in

the optimal ways, and create a case for increased investment in antibiotic research taking into account the needs of all countries.⁶ Furthermore, the CDC has taken this plan into account and has put four main actions into practice for preventing antibiotic resistance. These actions include preventing infections, tracking antibioticresistant infections and gathering information surrounding them, regulating the prescription of antibiotics, and working to develop new drugs.⁷ Antibiotic-resistant superbugs have become one of the main fears of the medical community in recent years. As antibiotic use has skyrocketed, humans have drastically increased the rate of naturallyoccurring antibiotic resistance in microbes. There are potential solutions to this problem, but until the prescription of antibiotics is regulated and

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new drugs are discovered or developed, superbugs could continue to ravage the world. The first step to preventing this, however, could be in the public’s hands. According to Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, “If [your doctor’s] prescribing the antibiotic, ask about the scientific basis,” Fauci said. “‘What kind of infection do I have? What makes you think it’s bacterial? What kind of bacteria is it and what makes this antibiotic good for this bacteria?’ There should be that kind of dialogue between a physician and a patient.”⁸

For references, please see Page 23

Genomic Sequencing: The Future of Medical Profiling By Thomas Dent

ecall the last time you went to the doctor’s office. Whether your physician was equipped with a tablet, a clipboard, or a computer screen, he or she was almost certainly looking at your personal health record. Your personal health record is a document containing information that has been deemed important for healthcare providers to know about you. Today, this profile includes your current medications and medical history, along with physiological data such as blood pressure and cholesterol readings.¹ Doctors use this information to guide their course of treatment for each patient. Although these documents contain valuable information, many believe that, not too long from now, a detailed analysis of our genetic makeup will act as the principal guide to our health profiles, giving both our health caregivers and ourselves a more holistic understanding of our health. But how can our genes inform our health care? The answer lies in the order of the nitrogenous base pairs

that are found in our DNA. The specific sequences of base ordering within our genes distinguish the biological makeup of one organism from another. Variations in base pair arrangements account for the myriad different ways that life forms appear on this planet, from transparent jellyfish to cognitively-inclined human beings.

99.5%. When considering the fact that each human genome is collectively comprised of about three billion base pairs, the number of differences that appears throughout various genetic sequences can amount to as much as ten million.² These alterations in base pairs are known as SNPs (pronounced ‘snips’), or single nucleotide polymorphisms. In recent years, geneticists, biostatisticians, and survey methodologists have collaborated to create ways of detecting SNPs to provide individuals with information about their genetic makeup, including their ancestry and potential predispositions to disease. One such team, a leader in the personalized DNA testing industry, is a California-based company called 23andMe. Run by CEO Anne Wojcicki, 23andMe’s 23andMe objective is to provide its Despite the drastic customers with a detailed differences we observe in genetic analysis based on a physical appearance even saliva sample and answers to an within our own species, the extensive questionnaire. percentage of the human genetic DNA is extracted from the sequence that is conserved from saliva and washed over a one person to the next is about customized version of Illumina’s

Science & Technology • Volume 9 • 7

HumanOmniExpress-24 format chip, which has DNA probes that latch onto complementary DNA sequences.³ The chip used can currently detect over 65,000 SNPs, and with the use of publicly available genome references, 23andMe is able to infer information about over 14 million other variants.⁴ While many patrons are primarily interested in the trivial phenotypic inferences that can be determined, like how probable it is that their child will have blue eyes, 23andMe’s research team has its ambitions set on other aspects of the analysis. The team has already set in motion a system that uses its genetic database in combination with the DNA and survey responses from their customers to find links between certain SNPs and corresponding phenotypes to correlate, for example, an abnormally high prevalence of a particular illness. With this, they are able to provide their customers with valuable information about potential health risks to which they are predisposed based on associations they have found. Sergey Brin, a co-founder of Google, was alarmed to see that his 23andMe results revealed the presence of the LRRK2 gene, located on the 12th chromosome.⁵ Previous biostatistical analyses and various association techniques have demonstrated that people

with this particular gene may be up to 75% more likely to develop Parkinson’s disease in their lifetime than those without this particular SNP.5 Unfortunately for Mr. Brin, not enough is known about Parkinson’s disease to suggest healthier lifestyle options to help prevent such an ailment.⁶ However, for a vast majority of inherited illness predispositions that 23andMe is able to detect,

links and a bigger database of genetic information to generate such links from, the team can detect more predispositions with higher accuracy, perhaps to the extent that such a test gives information about every aspect of the customer’s health and would therefore become a part of everyone’s medical profiles. As envisioned by its Director of Research, Joyce Tung, “someday, knowing your own

there are known ways to reduce the likeliness of occurrence and morbidity in the individual. In such instances, 23andMe is able to inform its patients of their increased probability of developing a certain condition, and then explain how they can alter their daily habits to minimize their chances of developing the ailments to which they are predisposed.⁷ It is this process of identification, followed up by informed preventative measures, that drives 23andMe to expand its database and inferential capabilities. With better technology to find

genetics is just going to be a part of your daily life, just the way that now people know about their cholesterol levels or blood pressure.”⁷ With this statement, Ms. Tung expresses her company’s vision to improve genomic sequencing to a point where the individual’s genome is relevant background information taken into account in everyday clinical interactions. Although the company began with promise, it experienced a setback when the FDA intervened in 2013. The FDA expressed its concern that 23andMe’s Personal Genome Service (PGS) was potentially

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providing its customers with either false positives or false negatives. According to Alberto Gutierrez, FDA’s Director of In Vitro Diagnostic Device and Safety, there is the danger that “patients relying on such tests may begin to self-manage their treatments through dose changes or even abandon certain therapies depending on the outcome of the assessment.”⁸ Additionally, some customers

For these reasons, the company experienced a twoyear lull in which its services were limited to giving ancestral feedback to its decreasing number of new customers. It was not until February of 2015 when the company got its first FDA approval to test for carriers of Blood syndrome, a disease which causes instability in DNA structure and thus an increased risk of developing cancer.⁴

23andMe

criticized that the use of surveys to complement the genetic tests was not a trustworthy aspect of the biostatistical association methods employed.⁹ Others realized that certain ethnic groups were underrepresented in the database and were therefore given results with potentially lower accuracy inferences.⁹ Furthermore, a former customer named Lisa Casey filed a five million dollar class action lawsuit against the company for providing its customers with health advice without validation from the FDA.10

By the end of the year, 23andMe provided sufficient evidence to the FDA to get approval to test for and provide feedback on 36 different ailments screened for in the saliva swabs it collects, with that number increasing every year.⁴ The company is now back on track in its pursuit of enhancing genomic sequencing to the extent that an entire human genome can be read and analyzed at a reasonable price. Although such an ambitious goal may seem unattainable considering the present day resources at the company’s

disposal, 23andMe’s biophysicist Arnab Chowdry believes that “next generation sequencing and all these technologies that are popping up [will] allow you to sequence the entire genome of an individual in a very short amount of time and [for] very cheaply.” With improvements in the company’s efficiency of computationally analyzing DNA, he envisions a “future where everyone’s genome is just part of your medical record.”11 The aspirations for the future of 23andMe’s sequencing capabilities and the role of genetics in medicine are both exciting and realistic. However, 23andMe is only one of many in the personalized DNA testing industry, as other companies including Color Genetics, Counsyl, and MyMedLab have also been granted rights to provide medical advice without the consent of a physician.12 This competition legitimizes the hope that an entire human genome can be personally sequenced and analyzed in the future. Most likely, no single company will be able to accomplish this goal by itself, yet with improving technologies and potential genetic database merges, we can perhaps expect genomic sequencing “to be that thing that informs your health care in the future.”11 For references, please see Page 23

Science & Technology • Volume 9 • 9

Deleting Disease with CRISPR Cas-9 By Troy Biermann and Srijit Paul

enetic conditions such as cystic fibrosis and sickle cell anemia have long affected humankind as untreatable and life-threatening diseases, but these could soon be issues of the past. Over the past two decades, gene therapy— the replacement of defective or missing genes with normal ones—has grown from an extremely experimental field to a burgeoning and increasingly influential area of study. As reference, annual NIH funding of gene therapy has grown exponentially from $58 million in 1991 to an estimated $250 million in 2017.¹ In particular, the creation and use of restriction enzymes such as zinc finger nucleases (ZFN) and transcription activator-like effector nucleases (TALEN) have been crucial to the emergence of gene therapy as a leading area of scientific inquiry. ZFN consist of two individual regions: a DNA-binding region, made up of two-finger, elongated proteins that can bind unique DNA sequences, and a DNA-cleaving region,

consisting of a FokI restriction endonuclease, a certain enzyme that can cut DNA and introduce a double strand break.² To completely isolate a specific sequence of DNA, the zinc fingers of the enzyme bond to their corresponding sequences of DNA, and the two

endonucleases cleave the DNA at the sites specific to t h e location and remove an entire section of DNA. The gap created by the removal of a specific DNA sequence is either replaced with additional DNA or eliminated altogether by fusing both sides of the gap. TALEN also utilize FokI restriction endonuclease proteins as a means of separating the DNA helix. However, instead of zinc fingers, TALEN have

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transcription activator-like effector proteins consisting of groups of amino acids that together recognize a specific DNA base, giving them more specificity than ZFN.³ TALEN have even been used to treat leukemia in two human babies, eventually helping both recover completely.⁴ Although ZFN helped to break the initial barrier between scientists and effective gene therapy, TALEN has revealed the nearly limitless possibilities behind editing human DNA. ZFN and TALEN

have been crucial to the proliferation of gene therapy, but it goes without saying that these methods have certain issues: both tend to struggle with efficiency, ease of design, and convenience.⁵ ZFN and TALEN both rely on specific protein and DNA recognition, and, as a result, are fairly expensive and time-consuming to create in a laboratory. Additionally, these

mechanisms prevent multiple genes from being replaced at the same time, ultimately making ZFN and TALEN somewhat ineffective at treating disorders that stem from more than one gene. One method that circumvents both of these issues has recently been on the rise: Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) Cas9. This new gene editing method has been highly touted by the scientific community as the future of gene editing. CRISPR-Cas9 was developed by Dr. Jennifer Doudna, who stated that CRISPR-Cas9 is based off an improvised immune system for bacteria. This immune system utilizes DNA between palindromic repeats in the genetic code to recognize invasive viruses, and upon identification, the bacteria’s special “cutting” Cas proteins can cut through and deactivate a strand of the virus’s DNA.⁶

These new discoveries led to the development of a more refined system called CRISPR-Cas9. The CRISPR-Cas9 system utilizes a Cas9 protein to cut the DNA strand. The CRISPR part of the system is guided by a RNA complex that is

composed of a single stranded RNA that matches the targeted gene and a double bonded RNA that holds the single stranded RNA to the Cas9 protein. With this method, the single stranded RNA sequence can be altered to fit with any DNA sequence and the Cas9 protein can be used to cut and deactivate a specific gene. The question that remains is whether or not CRISPR-Cas9 works in application beyond its seemingly straightforward theoretical application. There have been many experiments conducted to test the feasibility of CRISPR-Cas9. For example, in a study on zebrafish embryos, systems utilizing CRISPR-Cas9 performed just as well as the ZFN and TALEN systems and even managed to target two sites on the genome that ZFN could not.⁷ Another study on fruit flies concluded that genes modified by CRISPR-Cas9 could be passed down through fruit fly generations, suggesting that these genetic changes could positively affect an organism and its offspring permanently.8 Although CRISPR-Cas9 has yet to see widespread human clinical trials, it has shown great promise for applications in remedying human conditions. For example, CRISPR-Cas9 has been shown to fix the mutation that causes cystic fibrosis in

isolated human intestinal stem cells of patients afflicted with it.⁹ Even though these results may seem promising, there is more research and development that must be completed before it sees more widespread human application. A test of CRISPR-Cas9 on human tripronuclear zygotes, which are fertilized human eggs with an abnormal number of genes, resulted in proper cutting of a specific gene, but repair mechanisms in the cells failed to properly rectify the breakages, resulting in mutations.10 The future for CRISPR-Cas9 is bright. Its versatile approach and simple process make for an incredibly powerful medical tool. Since CRISPR is a new technology, the majority of scientific studies utilizing the technique have been limited to experimentation in vitro rather than in vivo. Like any new medical method, CRISPR will have to go through many rounds of experimental trials and rigorous evaluation before it is allowed to be used on humans. Although the fact remains that the concept of simply deleting disease-causing genes is quite some distance away, this discovery is an exciting step towards that goal.

For references, please see Page 23

Science & Technology • Volume 9 • 11

The Journey to a 523 By Shannon He

he MCAT is one of the defining episodes of the pre-medical experience. It can be daunting: months of study all culminating with a 7.5-hour long test that plays a large role in determining your future. However, it does not have to be so scary, or so stressful. I took the MCAT this past September (2016) after a summer of studying and scored a 523, which placed me in the 100th percentile.¹ I’m here to share my journey and some tips along the way to a successful MCAT. There were two phases to my three-month studying process. One, review of material and content, otherwise known as the “I probably didn’t study as much as I should have” phase. Two, studying flashcards and taking practice tests, otherwise known as the “Oh shoot, the test is only a month away” hardcore studying phase.

confident in both my knowledge of the material and that I wouldn’t procrastinate. But, if you know that you’d end up procrastinating too much, then a class could be helpful to keep you on track. After I purchased the books, it was official. I was studying for the MCAT. Advice #1: Start with the topics you find the most challenging.

I began by watching some biochemistry videos since my books hadn’t arrived yet. I realized that there were about a dozen pathways I hadn’t even heard of in class but needed to know. After receiving my books, I switched from biochemistry and turned to physics, the bane of my existence. I figured I should start with the subjects I felt least confident in (completely ignoring the fact that I had just stopped studying biochemistry). As I worked my way through the book, I took notes on all the formulas, common problems, and completed The weekend after finals, I short practice quizzes at the bought review books and the end of each section. I wasn’t accompanying online testing doing particularly well on the material. I decided not to take practice problems, but I was a class (neither in person nor making my way through the online) since I was pretty material at a good pace, which

Phase One: Content Review

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is the most important thing to staying on track during the content review phase.

Advice #2: Make sure to schedule yourself some “you” time, but in explicit quantities. The first weekend after I began studying, I took my first practice test to see my baseline score: 503. I was really impressed with myself ! I’d barely started studying, and I was already above a 500, which is just above the 50th percentile. I thought, “studying for this test will be easy.” Following the ego boost, I only did a few chapters of physics a day, studying for a maximum of about 6 hours each day. The rest of the day, I either worked in lab or relaxed. While I had previously made a promise to myself not to start any television series, I naturally broke that promise. Instead of taking practice tests on the weekends, that time became binge-watching time. Despite this, I finished the physics material in about a week and a half. But, as you may have guessed, I scheduled a little too much “me” time. Relaxation is an important process of studying for a test like this. If you spend the

whole three months studying, you’ll burn yourself out, which is counterproductive. In my opinion, any form of relaxation is good as long as you space it out evenly with your studying. For me, the ideal balance meant studying most of the day and taking lunch and dinner breaks to eat and watch an episode of television, and then relaxing a bit before going to bed to wind down. Naturally, other people’s ideas of relaxation can be different, but you should try to dedicate most of the day to studying while interspersing some “you” time in between. Advice #3: Don’t stress over practice exam scores if you don’t see improvement early in the process, just focus on the review process.

During week three, I reviewed biology. I reviewed physiological systems and took another practice test. I scored a 501. Those two small points made me regret spending so much time not studying. As practice exam review is an important part of the process, I spent a lot of time on the biochemistry section, where I had trouble, and re-reviewed all of the pathways and molecules. I didn’t fully understand everything, but at least I was familiarizing myself with them. At this point, one month had passed. A part of my brain set off some alarms yelling, “Your score got worse! Study harder!”

Despite this, I tried to remain calm, because I knew I hadn’t covered all the material yet. Next, I studied chemistry and powered through, only taking about a week to review it. After chemistry, I studied for psychology and sociology for two weeks. While these sections required a lot of rote memorization, the content itself was not as challenging as the sciences were to me. I took another practice test. Now that I’d done one study pass through all the material, I thought my score would skyrocket. 505. It was an improvement, but barely. It wasn’t exactly the encouragement I wanted, but it was something. Though I didn’t feel particularly comfortable with any subject yet, I felt I had set myself up well for my next phase of studying.

Phase Two: Flashcards, Practice Tests

Advice #4: Make a schedule for yourself and follow the suggested test day routine. In the last week of the second month, I made online flashcards for the biology and chemistry/physics sections and my friend made flashcards for the psychology and sociology section, and we shared them with each other. For the month leading up to the test day, I holed up at home to study. I planned

a study schedule for the month and followed it faithfully. I modeled my daily schedule after the actual test day. I woke up and started studying at the test start time, 8 AM. I timed my lunch and ate a sandwich, the lunch I had planned for the test date. I usually worked until about 9 pm. Importantly, after the long hours of studying, I always made sure to relax for at least half an hour before going to bed. Following the testing schedule is a good strategy for shifting your body clock to being productive for a large chunk of time. Additionally, studying around the framework of the exam questions gets you used to the timing of the sections and the mental exhaustion of taking a test for 8 hours. I studied two sets of flashcards every day, and I made sure to talk through the pathways and terms out loud. Additionally, I wrote out all the equations even if I thought I knew them. I studied each set several times, which took a lot of time. Advice #5: Keep taking practice tests.

Every two to three days, I would take a practice test starting at 8 AM and then do a set of flashcards in the evening. 508. 509. I was getting better! 504. 504. 505. That worried me. I had heard that third party test prep companies like the one I was using made their practice tests harder than the actual exam, but hearing it and believing it

The Medical Experience • Volume 9 • 13

were two different things. I had finally mustered up the courage to take a real AAMC practice test, the most comparable to the actual exam. I scored a 517, and that was exactly what I needed to see to keep my confidence up. It’s important to keep taking practice tests to get into the rhythm of the exam and to hone your test taking strategy and skills. Advice #6: Relax before the test.

I took my last practice test the Tuesday before my Saturday exam. Over the next couple of days, I went through my flashcards and did some AAMC practice problems. I didn’t overwork myself because I wanted to give my brain a rest. The night before the test, I went to sleep at 10 PM and I woke up the next morning at 5:45 AM. Advice #7: Stay calm on test day, take it all in stride.

The actual test felt like every practice test I had taken except for the fact that the computers disconnected for everyone in the room twice. It was frustrating that it broke me off in the middle of a passage or a problem, but I made the best out of it by taking the time to walk around and drink some water. If things go wrong during your test, try not to worry, and use the time to clear your mind. Finally around 5 PM, due to technical difficulties and the

proctors starting late, I finished. I felt so relieved that I could relax without being tethered to studying. Advice #8: Relax after test day, you did everything you could!

I felt a bit peeved that some of the things I had studied for didn’t come up on any of the questions. But it wasn’t worth worrying about. I had done all I could. Reflecting on it afterward, I’d summarize the test-taking approach as such: you have to make sure you get the questions you actually studied for right. For the random questions that you couldn’t possibly have

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known to study for, you just have to guess them well. It sounds scary to approach a test like the MCAT with some guesswork and luck, but your test-taking skills can carry you a long way. The day the scores came out, I was worried I would have to take the test again. When I opened my score of a 523, I was relieved. It reminded me to have confidence in myself. My journey to my desired score on the MCAT wasn’t a smooth one, but sticking to a schedule, balancing your life, and simply believing in yourself can bring your desired score well within your reach. For references, please see Page 23

What I Wished I Asked The things I should have asked during my medical school interviews By Sarah Smith Editor-in-Chief Emeritus

f you Google, “How to questions you will ask students, you will become: professors who prepare for a medical school professors, and administrators teach you physiology, faculty interview,” almost every advice you meet on campus. If you’re any- who teach you “doctoring,” menwebsite tells you to have your own thing like how I was, you may feel tors who help grow your pasquestions prepared to ask your unsure about what questions will sions, and deans who make deinterviewer, because most medical help you truly differentiate between cisions on behalf of the students. school interviewers will ask you, medical schools. It’s important to It is important to know how the “Do you have any questions for reflect on your personal values, students feel about the adminisme?” so you can ask the right questions tration, and whether or not they When I was applying for to figure out the best fit for you. feel that the faculty are open, approachable, and supportive. Ask medical school, I didn’t think medical students if their promuch about this question. I fessors and faculty are recepprepared a generic question tive to student shadowing or or two about an aspect of the "It's important to student research assistants, curriculum I had researched before, or a club I found reflect on your personal and if it is easy to approach them about these things. interesting on the school’s values, so you can ask website. Speaking to my M1 2) Is the administration peers, many of them did the the right questions..." responsive to student feedsame thing. back? In retrospect, there are so many questions I wished I With schools constantly evolvhad asked during the process. ing and adapting to meet the In general, all medical schools needs of the health care field, strive for the same things: diverse Here is a list of 6 questions that there are bound to be changes students, well-balanced curricula might give you insight into the in the curriculum during your andopportunities for research. less obvious qualities that shape time in medical school. Some of It is the less tangible qualities, a medical school experience: these changes will be smooth and the the ones that are felt and well-received, but others may be observed rather than written on 1) What is the student- faculty bumpy with room for improvea website, that truly differentiate dynamic like? ment. It’s important to know how medical school cultures. Medical school faculty plays a huge responsive the administration With second look season role in your medical school expe- is to student opinions and feedcoming up, it’s a good time rience. These are the people who back and whether there are systo start thinking about what will shape what kind of physician tems in place for your voice to be

The Medical Experience • Volume 9 • 15

heard. For example, ask if there is a feedback system for things like lectures, small groups, and required clinical experiences and whether or not changes are made based on the feedback received. 3) How many student organizations are there, and how easy is it to start one?

In medical school, it’s important to balance the academics with extra curriculars that you love and activities that get you out of the library and make you feel energized and recharged. This can be anything from IM sports, to a book club, to a mentorship program for nearby high school students. If you’re someone who values innovation, ask about opportunities to start your own clubs or initiatives. If you’re interested in the cross section between health and another field, ask about collaboration with other graduate schools or institutions. This is your chance to see what students are passionate about and what kinds of resources there are to follow your passions. 4) Is the school true pass/ fail?

Most schools have converted to a pass/ fail grading system for the first year of medical school. But this can be nuanced: some schools still do high pass or low pass, whereas other schools still have

an internal ranking system. It’s valuable to reflect on what kind of atmosphere you will do best in. Some people like competition and being held to scores, while others prefer to have a true pass fail system to alleviate some of the pressure of the first year. Ask medical students about the grading system, and think about what system would be best for you.

5) What is the exam schedule like? This is a huge part of your medical school experience, and something that I personally never took the time to consider when choosing a school. Some schools quiz every single week; others just have a final exam for sequence. Some schools have flexible quizzing, where exams open on Friday and you have until Sunday night to take the exam. Some students like the accountability of weekly evaluations, while others like the flex-

16 • The Medical Decoder • Spring 2017

ibility that comes with only having one final. There are pros and cons to all exam schedules, but it’s helpful to think about what kind of testing pattern you prefer. 6) What does community look like at your medical school?

Medical school is a challenging, busy, demanding, and rewarding endeavor. There will be times when medical school feels overwhelming and all-consuming. For me, having a support system and community to lean on is what gets me through the hardest times, but I didn’t really think to ask about this on the interview trail. Building community can take many forms: medical school sponsored dinners, wellness and self-care events, social events on the weekends, or support groups for mental health. At my medical school, you learn “doctoring” with a group of 10 students, and you work with the same group for all 4 years; this makes a smaller community of support within the larger school. Think about what community means to you and what you need from a community, and don’t be shy about asking medical students what community means to them.

Medical Voluntourism Good for your resume, bad for the community? By Eric Kim Editor-in-Chief

rior to departure, I envisioned leaving a great, long-lasting mark on the community that I would serve—some accomplishment that would dramatically impact the lives of the local people. I would become a star volunteer, solving a riddle that has troubled my NGO and the community for years. Perhaps, I would even get to learn about and observe directly how medicine is practiced in Uganda. A dreamy-eyed sophomore, I landed in Entebbe Airport in the sweltering heat of a Ugandan summer, unaware of my naiveté and self-centeredness at the time. “Voluntourism,” a term that combines volunteerism and tourism, comes in many flavors, but it has a common recipe: good intentions, ill preparation, and a net harm on the local community. A 2008 study estimated that 1.6 million voluntourists spend an astounding $2 billion annually.¹ These highly motivated individuals are attracted to the prospect of “making a difference” and embark upon a journey to Kenya, Haiti, or any other developing country. In theory, these individuals help those in need while experiencing a dramatically different reality and broadening their horizons. However, these shortterm visits by well-meaning visitors have created unintended and unforeseen problems. Particularly alarming is medical voluntourism, in which

premedical students, medical students, or simply curious people travel to developing countries and participate in medical procedures that they have no proper training for. One high-profile example in 2008 came from Tim Tebow, a

professional football player at the time, who embarked on a weeklong trip to an orphanage in the Philippines. At the orphanage operated by his father’s ministry, Tebow assisted in and even performed circumcisions and surgeries on local children. In an interview with the Orlando Sentinel after his journey, Tebow proudly stated: "The first time, it was nerve-racking…Hands were shaking a little bit...You can't do those kinds of things in the United States. But those people really needed the surgeries. We needed to help them."² His statement that any help—

even from someone who has no training or credentials—is better than nothing represents the most problematic aspect of medical voluntourism. It is certainly true that sub-Saharan African countries are in dire need of medical professionals: while an astonishing 24% of disease burden worldwide is located in sub-Saharan Africa, only 3% of healthcare workers in the world reside in the area to deal with the health crises.³ However, a shortage of trained medical personnel does not mean people with no qualifications should fill it. Dr. Jessica Evert, a practicing physician and co-chair of Global Activities by Students at PreHealth Level (GASP), recounts her own experience in Kenya during her first year in medical school, when she was asked to perform a lumbar puncture on a child: “The child cried. He was held down and there was no anesthetic. I ended up not doing the procedure right so it delayed his diagnosis.”⁴ Although no statistics exist, Dr. Evert’s anecdote is one of the many examples that demonstrate the potential harm of well-intentioned but misguided medical voluntourism. In her book, Dr. Noelle Sullivan, a professor of anthropology at Northwestern University, recalled a conversation with a Tanzanian physician who asked her a question that lies at the heart of this phenomenon: “Would it

The Medical Experience • Volume 9 • 17

be permitted for mgeni (random guests) to enter and watch or do any surgical procedure they wanted where you live?”⁵ Currently, these international programs seem to prioritize foreign visitors’ motivations over the needs of the local population. For many, these overseas programs offer opportunities not readily available back home. Unlike in their own countries where strict laws largely restrict their hands-on exposure to clinical procedures, these volunteers gain unlimited access overseas. Often encouraged by the local staff, volunteers could deliver babies, set bones, and perform surgeries on a regular basis.⁵ These experiences all constitute “clinical experience,” a vague term that many seek for entry into medical school. Medical programs ask applicants to gain clinical experience through volunteering or shadowing to ensure that applicants understand and are ready for what is required of physicians. In search of such experience, some students see these overseas programs as a way to bolster their application. One statement by a volunteer in Tanzania echoed this pre-professional incentive: “I’ve never been to Africa, and I thought it would be a good experience; and on top of that, you volunteer so you’re helping people and it doesn’t look too bad on your resume.”⁵ Most volunteers speak of their desire to serve and “help.” It is not wrong to seek professional fulfillment as an added bonus in pursuit of meaningful change and altruism. However, by prioritizing their own experiences over the well-being of

patients, medical voluntourists flout the tenets of beneficence (a physician’s obligation to act in the best interest of the patient) and non-maleficence (doing no harm). Just as important, these short-term visitors often lack the necessary understanding of the developing country’s culture. The motivations of the host medical organizations in the developing world further bolster this dangerous phenomenon. First and foremost, organizations receive fees for every foreign volunteer they host that are then used to repair facilities and purchasing supplies and other necessities. Reliance on these funds has pressured medical personnel of the host organizations to keep the volunteers engaged and, as one expert put it, “entertained.”⁴ To meet the desires and expectations of the visitors, physicians invite the visitors to participate in the procedures, in spite of established hospital policies or laws. Secondly, many hospitals hope that the relationships they build with volunteers will extend beyond the duration of their stay and lead to either personal or institutional advancements. For example, one administrator hoped that hosting volunteers could lay the groundwork for bringing orthopedic surgery to the hospital, although such institutional improvements rarely come to fruition.⁵ Under the guise of altruism and international development, medical voluntourism endangers people of the developing world and instills wrong ideas in these visitors, many of whom are aspiring health professionals. The trend of allowing untrained

18 • The Medical Decoder • Spring 2017

foreigners to engage in medical practices in the developing countries is built on the unspoken notion that the lives of those in the developing world can be objects of experimentation. However, one can still have a beneficial, productive overseas volunteering experience. Foreign volunteers must first realize that the primary goal should be to learn, not to “help” or to “teach.” In our two months in Uganda, my team and I actually worked with the social services department of a HIV/AIDS clinic and organized workshops teaching urban farming techniques to jajjas—grandmothers who adopted their grandchildren after their own children had passed because of AIDS. Although agriculture was not our original area of interest, we gained invaluable insights into the issues surrounding developing countries and the complex webs of culture, economics, and health through our project. More importantly, we learned the values of compassion and teamwork from our supervisors and the community of jajjas. Even if the volunteers do not get the desired “clinical experience,” they will learn about global health inequity, relationships between patients and healthcare providers, and the role of medicine in different settings. Instead of expecting to make “a difference,” volunteers should expect the host country, local workers, and organic experiences to make a mark on them. With mutual respect and appreciation, both the volunteer and the host country can benefit from a mutually beneficial exchange of ideas, cultures, and friendships. For references, please see Page 23

Pharmaceutical Prices: Formulating a Cure By Nathan Shlobin

n August 2015, Turing Pharmaceuticals acquired Daraprim, a drug used to treat toxoplasmosis, a life-threatening parasitic disease that can cause miscarriages and stillbirths in pregnant women and cause severe fevers and contusions in patients with weakened immune systems. In a move that critics labeled price-gouging, but Turing CEO Martin Shkreli described as necessary, Turing raised the price of the medication from $13.50 to $750 per pill, setting off a firestorm.¹ While Turing proceeded to lower the price of Daraprim following the complaints, the new price remained 2,500% higher than before the price increase.² This series of events is far from unique, but it elucidated a problem in healthcare that had previously gone undetected: the rising cost of pharmaceutical drugs. When pharmaceutical companies raise the prices of their drugs, at first, insurers bear the burden of the extra cost. For example, over the course of an eighteen-month period during which numerous EpiPen price increases occurred, the

mean price insurers paid for an EpiPen pack rose from $421 to $635.³ However, insurers soon transfer the extra cost to consumers by raising premiums, deductibles, or coinsurance costs, or refusing to cover the cost of the drug altogether. When Turing Pharmaceuticals increased the price of Daraprim, some patients were forced to pay coinsurance costs of $6,000, even up to $16,830.⁴ Disquietingly, insurance – put in place specifically to prevent consumers from accruing

massive medical costs – fails to protect consumers. Stemming from the inadequate protection of insurance, price hikes decrease access to pharmaceuticals.⁵ Pharmacies are often unwilling to stock expensive drugs for fear of financial loss if the drugs are not purchased. When consumers have access to the drugs they need, they are often unable to purchase them due to their high prices. Patients are left with a choice: avoid purchasing the medication they need or

Health Care & Policy • Volume 9 • 19

purchase the medication at a prohibitively expensive price. Part of the reason pharmaceutical companies continue to increase the prices of their drugs is the lack of leverage on pharmaceutical companies by purchasers of pharmaceuticals. Most significantly, Congress explicitly prohibited Medicare from negotiating prescription drug prices with pharmaceutical companies in 2003.⁶ This decision is problematic because Medicare is the largest buyer of prescription drugs in the United States.⁷ Additionally, many different employers, hospitals, insurance companies, and governments purchase drugs separately. Since they do not cooperate with each other to increase their collective buying power, their individual effect is minimal. In contrast, the governments of many European countries directly negotiate prices with pharmaceutical companies. For example, the United Kingdom’s National Health Service purchases drugs for the entire country’s supply.⁸ The National Health Service maintains significant buying power, leading to lower costs for the citizens of the United Kingdom. Another reason that pharmaceutical companies raise their prices is the absence of generic counterparts for many brand name drugs. For example, the EpiPen holds 90% of the automatic

epinephrine injector market.⁹ One cause of the lack of competition is long exclusivity periods, lengths of time during which only the initial developer of a medication can sell the medication. Exclusivity periods provide for temporary government-issued monopoly that allows pharmaceutical companies to set prices at the level of their choosing without pushback. The lethargic and costly review process for new drugs by the Food and Drug Administration also plays a role. Researchers must demonstrate that their generics are the same in composition and effect as their brand name counterparts through a plethora of studies. The inefficiency is so extreme that the Food and Drug Administration approved zero generic drugs out of nearly 1,600 submitted by the end of fiscal year 2014.10 It is imperative that policymakers take concrete action to protect consumers. As Jeremy Green, MD, PhD, an Associate Professor at the Johns Hopkins School of Medicine who researches the history of the pharmaceutical industry, argues, “addressing monopolistic conditions that give rise to sudden price hikes is a means ‘to prevent future shortages’.”10 Action is crucial for the future stability of healthcare in the United States. Allowing Medicare to negotiate drug

20 • The Medical Decoder • Spring 2017

prices and facilitating the consolidation of buying power among the smaller purchasing entities will ensure that pharmaceutical companies do not continue unchecked. Decreasing exclusivity periods and simplifying the complex new pharmaceutical approval process will provide for more competition in the market. Together, these actions will lower prices, changing the paradigm within the healthcare industry and safeguarding access to and the affordability of drugs that people require for the single most important element of their lives – their health.

For references, please see Page 23

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Medical Error W

hen a friend or a loved one enters the hospital seeking treatment, a primary concern is that the disease progression has gone too far for effective treatment and has caused long term damage to the body. The primary concern is rarely a mistake on the hospital’s part: a medical error. Medical error can be defined as “an act of omission or commission in planning or execution that contributes or could contribute to an unintended result.”¹ The definition of medical error depends on a few key ideas. First, a doctor should not be blamed for a bad outcome, or a worsened patient condition, if there was no mistake in planning or execution. Second, if incorrect protocol is used, the

occurrence should be treated as medical error even if the patient’s condition did not necessarily worsen as a result. Finally, a doctor should not be blamed for a mistake that has no chance of creating a bad outcome. A simple example of this would be a doctor facing a malpractice suit for spilling water on a patient who died of cancer shortly thereafter. However, this last idea is often the source of much confusion. Who can truly say what the source of death was, especially when multiple diseases had developed? Who can say that a patient would have survived had it not been for this small error? This uncertainty has led to much disagreement over what should be and should not be called

by Karol Bisaga

medical error. This debate has only fueled researchers’ desire to quantify it. Medical error first entered the public consciousness in 1991 with a study published in the New England Journal of Medicine claiming that medical error was a significant cause of adverse effects, with a little more than 1% of all the patients visiting hospitals in New York State in 1984 affected.² A larger study named “To Err is Human,” conducted by the U.S. Institute of Medicine and published five years later, claimed that between 44,000 to 98,000 people die from errors every year.³ This publication was the first to name the error epidemic and ignited several movements among hospitals and government agencies to

Human Interest • Volume 9 • 21

eeeejjjffffff pinpoint and eliminate these errors. One of these programs, initiated by the Institute for HealthCare Improvement, was called “The 100,000 Lives Campaign,” in which an independent agency rewards hospitals that pledge to improve or maintain patient safety standards. As of 2016, the campaign has purportedly saved 122,300 lives, a figure disputed by some, again due to its indeterminate nature.⁴ The Healthcare Research and Quality Act of 1999 was also passed as a result of the 1984 report and established the Agency for Healthcare Research and Quality (AHRQ), a government agency that today commands a budget of $334 million annually. The AHRQ has also claimed to have saved 50,000 lives and prevented 1.3 million harms to patients over a three year time span but also admitted that the causes of these improvements are “not fully understood.”⁵ This brings us to the current state of affairs in 2017. Has patient safety worsened, or have the initiatives succeeded? In a 2011 report, the authors of Crossing the Quality Chasm, a study which outlined the “roadmap” for hospitals moving

forward, stated that progress has been greater than expected in some areas but “glacially slow” in others. They cited specific frustrations with a healthcare system that still is not “patient centered” and the “stubbornly high” rate of preventable harm.⁶ A recent study published by The BMJ that fueled headlines in outlets such as The Washington Post, CNN, and Time states that medical errors are the third leading

patient safety have empowered patients. These advances have made it possible for them to be proactive about medical error concerns by providing platforms on which they can research all options. The Center for Medicare and Medicaid Services has launched “Hospital Compare,” a website that allows patrons to access statistics concerning the hospital's record with certain procedures, such as heart surgery, birthing, and endoscopy.13 M e d i c a l error remains a prevalent problem in the medical community. When seeking treatment, asking questions and understanding one’s treatment plan can help prevent error. Though this article serves to enlighten readers, as always, the benefits of medical care far offset its dangers.

The expansion of health care and drug provider websites makes information regarding treatment and drugs just a click away. cause of deaths in the U.S., although this article has faced criticism for not conducting new research and simply taking data from older sources.7,8,9,10,11 Hospitals and healthcare groups are still joining the error prevention movement as enthusiastically as ever, with the Center for Medicaid and Medicare Services recently having awarded $347 million to hospitals with improving patient safety standards.12 Although it is hard to judge the exact likelihood of medical error, new expansions to the world of

22 • The Medical Decoder • Spring 2017

For references, please see page 23.

Superbugs on the Rise

REFERENCES

1. CDC’s Role. (2013). Retrieved January 29, 2017, from https://www.cdc.gov/drugresistance/cdc_role.html 2. Arias, C. A., & Murray, B. E. (2009). Antibiotic-Resistant Bugs in the 21st Century – A Clinical Super-Challenge. New England Journal of Medicine, 360(5), 439-443. doi:10.1056/NEJMp0804651 3. Branswell, H. (2017). A Nevada woman dies of a superbug resistant to every available antibiotic in the US. STAT. Retrieved February 19, 2017, from https://www.statnews.com/2017/01/12/nevada-woman-superbug-resistant/ 4. Spellberg, B., Guidos, R., Gilbert, D., Bradley, J., Boucher, H. W., Scheld, M. W., Bartlett, J.G. Edwards, J. (2015). The Epidemic of Antibiotic-Resistant Infections: A Call to Action for the Medical Community from the Infectious Diseases Society of America. Clinical Infectious Diseases, 46(2), 155-164. doi:10.1086/524891 5. National Institute of Health. (2016). Estimates of Funding for Various Research, Condition and Disease Categories. Retrieved February 19, 2017, from https://report.nih.gov/categorical_spending.aspx 6. World Health Organization. (n.d.). Global Action Plan on AMR. Retrieved January 29, 2017, from https://www.who.int/ antimicrobial-resistance/global-action-plan/en/ 7. Center for Disease Control. (2016). Measuring Outpatient Antibiotic Prescribing. Retrieved January 29, 2017, from https://cdc. gov/getsmart/community/programs-measurement/measuring-antibiotic-prescribing.html 8. Beck, J. (2015). Antibiotic Resistance Is Everyone's Problem. Retrieved March 19, 2017, from https://www.theatlantic.com/health/ archive/2015/06/how-to-stop-prevent-antibiotic-resistance-resistant-bacteria/397058/

Genomic Sequencing: The Future of Medical Profiling

1. Nourie, C. E. (Ed.). (2015). Your Medical Records. Retrieved April 04, 2017, from http://kidshealth.org/en/teens/medical-records. html 2. [23andMe] (2012). Genetics 101 (Part 1 of 5): What are genes?. [Video File]. Retrieved March 09, 2017, from https://www. youtube.com/watch?v=ubq4eu_TDFc. 3. 23andMe. (n.d.). Understanding the different versions of the 23andMe genotyping chip. Retrieved March 09, 2017, from https:// customercare.23andme.com/hc/en-us/articles/218392668-Understanding-the-different-versions-of-the-23andMe-genotyping-chip 4. Servick, K. (2015). CGS : Can 23andMe have it all? Retrieved March 05, 2017, from http://www.geneticsandsociety.org/article. php?id=8888 5. Goetz, T. (2010). Sergey Brin’s Search for a Parkinson’s Cure. Retrieved March 09, 2017, from https://www.wired.com/2010/06/ ff_sergeys_search/all/1 6. WebMD. (n.d.). Prevention of Parkinson's Disease. Retrieved March 09, 2017, from http://www.webmd.com/parkinsons-disease/ tc/parkinsons-disease-prevention 7. 23andMe. (2014). Retrieved March 08, 2017, from https://www.youtube.com/watch?v=jpm4T2-v_bw 8. Holpuch, A. (2013). FDA orders genetics company 23andMe to cease marketing of screening service. Retrieved March 09, 2017, from https://www.theguardian.com/science/2013/nov/25/genetics-23andme-fda-marketing-pgs-screening 9. FlourishAnyway (2016 ). The Risks and Benefits of 23andMe DNA Analysis. Retrieved March 08, 2017, from https://healdove.com/ misc/Should-I-Get-At-Home-Genetic-Testing 10. O'Connor, L. (2013). 23andMe Faces $5 Million Lawsuit Days After Being Banned By FDA. Retrieved March 19, 2017, from http:// www.huffingtonpost.com/2013/12/04/23andme-lawsuit_n_4387699.html 11. 23andMe (2014). Genetic Research. [Video File]. Retrieved March 09, 2017, from https://www.youtube.com/watch?v=ZEp8dFJ0Fw&t=5s. 12. Schmidt, S. (n.d.). 9 Leading Companies in Direct-to-Consumer Genetic Testing. Retrieved March 20, 2017, from http://blog. marketresearch.com/9-leading-companies-in-direct-to-consumer-genetic-testing

Deleting Disease with CRISPR Cas-9

1.U.S Department of Health and Human Services (2016). Estimates of Funding for Various Research, Condition, and Disease Categories (RCDC).Retrieved from https://report.nih.gov/categorical_spending.aspx 2. Gaj, T., Gersbach, C. A., & Barbas, C. F. (2013). ZFN, TALEN and CRISPR/Cas-based methods for genome engineering. Trends in Biotechnology, 31(7), 397–405. Retrieved from https://doi.org/10.1016/j.tibtech.2013.04.004 3. Deng, D., Yan, C., Wu, J., Pan, X., & Yan, N. (2014). Revisiting the TALE repeat. Protein & Cell, 5(4), 297–306. Retrieved from https:// doi.org/10.1007/s13238-014-0035-2 4. Qasim, W., Zhan, H., Samarasinghe, S., Adams, S., Amrolia, P., Stafford, S., … Veys, P. (2017). Molecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells. Science Translational Medicine, 9(374). Retrived from https://doi.org/10.1126/ scitranslmed.aaj2013 5. Nemudryi, A. A., Valetdinova, K. R., Medvedev, S. P., & Zakian, S. M. (2014). TALEN and CRISPR/Cas Genome Editing Systems: Tools of Discovery. Acta Naturae, 6(3), 19–40. 6. Doudna, J. A., & Charpentier, E. (2014). The new frontier of genome engineering with CRISPR-Cas9. Science, 346(6213), 1258096.

References • Volume 9 • 23

REFERENCES

Retrieved from https://doi.org/10.1126/science.1258096 7. Hwang, W. Y., Fu, Y., Reyon, D., Maeder, M. L., Tsai, S. Q., Sander, J. D., … Joung, J. K. (2013). Efficient In Vivo Genome Editing Using RNA-Guided Nucleases. Nature Biotechnology, 31(3), 227–229. Retrieved from https://doi.org/10.1038/nbt.2501 8. Yu, Z., Ren, M., Wang, Z., Zhang, B., Rong, Y. S., Jiao, R., & Gao, G. (2013). Highly Efficient Genome Modifications Mediated by CRISPR/ Cas9 in Drosophila. Genetics, 195(1), 289–291. Retrieved from https://doi.org/10.1534/genetics.113.153825 9. Schwank, G., Koo, B.-K., Sasselli, V., Dekkers, J. F., Heo, I., Demircan, T., … Clevers, H. (2013). Functional Repair of CFTR by CRISPR/ Cas9 in Intestinal Stem Cell Organoids of Cystic Fibrosis Patients. Cell Stem Cell, 13(6), 653–658. Retrieved from https://doi. org/10.1016/j.stem.2013.11.002 10. Liang, P., Xu, Y., Zhang, X., Ding, C., Huang, R., Zhang, Z., … Huang, J. (2015). CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes. Protein & Cell, 6(5), 363–372. Retrieved from https://doi.org/10.1007/s13238-015-0153-5.

The Journey to a 523

1. Summary of MCAT Total and Section Scores (2017). Published by Association of American Medical Colleges. Retrieved January 27, 2017, from https://aamc-orange.global.ssl.fastly.net/production/media/filer_public/dd/ae/ddaeef9d-6463-4bcd-82cc4aebc8b9ce39/mcat_total_and_section_score_percentile_ranks-update_with_n.pdf

Medical Voluntourism

1. Tourism Research and Marketing, European Association for Tourism and Leisure Education, Tourism Research and Marketing. (2008). Volunteer tourism: a global analysis: a report. Arnhem, The Netherlands: ATLAS. 2. Curtis, D. (2008). Florida Gators star quarterback Tim Tebow’s legend grows when ‘Dr. Tebow’ assists with surgical procedures on a missionary trip to the Philippines. Orlando Sentinel. Retrieved from http://articles.orlandosentinel.com/2008-05-05/sports/ tebow05_1_tim-tebow-philippines-general-santos-city 3. Spearman, C.W., Sonderup M.W. (2015). Health disparities in liver disease in sub-Saharan Africa. Liver International, 35(9), 20632071. doi: 10.1111 4. The Stream - Medical volunteerism [Video file]. Retrieved from https://www.youtube.com/watch?v=sQQJi0zI6T4 5. Sullivan, N. (2016). Volunteer Economies: The Politics and Ethics of Voluntary Labour in Africa. R. Prince, H. Brown (Eds.). Boydell & Brewer, Limited.

Pharmaceutical Prices: Formulating a Cure

1. Kroll, D. (2015). Imprimis' Fight Against Martin Shkreli Is Part Of A Larger Battle. Retrieved from http://www.forbes.com/sites/davidkroll/2015/10/23/imiprimis-ceo-on-compounding-a-low-cost-alternative-toturings-daraprim-for-toxoplasmosis/#798214a64af6 2. Long, H. (2016). What happened to AIDS drug that spiked 5,000%. Retrieved from http://money.cnn.com/2016/08/25/news/ economy/daraprim-aids-drug-high-price/ 3. Pollack, A. (2016). Mylan Raised EpiPen’s Price Before the Expected Arrival of a Generic. Retrieved from http://www.nytimes. com/2016/08/25/business/mylan-raised-epipens-price-before-the-expected-arrival-of-a-generic.html 4. Johnson, C. Y. (2016). How pharma bro Martin Shkreli described his own drug price hike: 'Almost all of it is profit.' Retrieved from https://www.washingtonpost.com/news/wonk/wp/2016/02/02/how-pharma-bro-martin-shkreli-described-his-own-drug-pricehike-almost-all-of-it-is-profit/ 5. Whitehead, N. (2015). Doctors Press For Action To Lower 'Unsustainable' Prices For Cancer Drugs. Retrieved from http://www.npr. org/sections/health-shots/2015/07/23/425387299/doctors-press-for-action-to-lower-unsustainable-prices-for-cancer-drug 6. Mohammed, R. (2015). It's Time to Rein in Exorbitant Pharmaceutical Prices. Retrieved from https://hbr.org/2015/09/its-time-torein-in-exorbitant-pharmaceutical-prices 7. Whalen, J. (2015). Why the U.S. Pays More Than Other Countries for Drugs. Retrieved from http://www.wsj.com/articles/why-theu-s-pays-more-than-other-countries-for-drugs-1448939481 8. Kounang, N. (2015). Pharmaceuticals cheaper abroad because of regulation. Retrieved from http://www.cnn.com/2015/09/28/ health/us-pays-more-for-drugs/ 9. Clarke, T. (2016). U.S. lawmakers blast Mylan CEO over 'sickening' EpiPen price hikes. Retrieved from http://www.reuters.com/ article/us-mylan-nl-epipen-congress-idUSKCN11R2OG 10. Hiltzik, M. (2016). The FDA can single-handedly reduce drug price-gouging. Why is it waiting? Retrieved from http://www. latimes.com/business/hiltzik/la-fi-mh-the-fda-can-single-handedly-stop-20160105-column.html

Medical Error

1. Grober, Ethan D., and John M.A. Bohnen. (2005). Defining Medical Error. Canadian Journal of Surgery, 48(1), 39-44. 2. Brennan, Troyen A. (1991). Incidence of Adverse Events and Negligence in Hospitalized Patients Results of the Harvard Medical Practice Study I — NEJM. New England Journal of Medicine, 324(6), 370-376. doi:10.1056/NEJM199102073240604.

24 • The Medical Decoder • Spring 2017

REFERENCES

3. Kohn, Linda T., Janet M. Corrigan, and Molla S. Donaldson. (2000). Read "To Err Is Human: Building a Safer Health System [E-reader Version]. Retrieved from http://neurosurgery.ucsf.edu/tl_files/NS_Main/QI/IOM_To%20Err%20is%20Human.pdf. 4. Wachter, R. M., and P. J. Pronovost. (2006). The 100,000 Lives Campaign: A Scientific and Policy Review. The Joint Commission Journal on Quality and Patient Safety, 32(11), 621-627. doi: http://dx.doi.org/10.1016/S1553-7250(06)32080-6. 5. Department of Health and Human Services. . (2016). Justification of Estimates for Appropriations Committees. Administration for Children and Families. 6. McKinney, Maureen. (2011). About that quality chasm. 10 years after IOM report, authors see progress, but... Modern Healthcare, 41(8), 38-9. 7. Martin, Makary, and Michael Daniel. (2016). Medical Error—the Third Leading Cause of Death in the US. The BMJ. Retrieved October 24, 2016, from http://www.bmj.com/content/353/bmj.i2139. 8. Christensen, Jen, and Elizabeth Cohen. (2016). Medical Errors May Be Third Leading Cause of Death in the U.S. CNN. Retrieved October 24, 2016, from http://www.cnn.com/2016/05/03/health/medical-error-a-leading-cause-of-death/. 9. Cha, Ariana Eunjung. (2016). Researchers: Medical Errors Now Third Leading Cause of Death in United States. The Washington Post. Retrieved April 22, 2017, from https://www.washingtonpost.com/news/to-your-health/wp/2016/05/03/researchers-medicalerrors-now-third-leading-cause-of-death-in-united-states/. 10. Oaklander, Mandy. (2016). Medical Errors Are the Third Leading Cause of Death: Study. Time. Retrieved April 22, 2017, from http://time.com/4316818/leading-cause-of-death-medical-errors/. 11. Gorski, David. (2016). Are Medical Errors Really the Third Most Common Cause of Death in the U.S.? Science Based Medicine. Retrieved October 24, 2016, from https://sciencebasedmedicine.org/are-medical-errors-really-the-third-most-common-cause-ofdeath-in-the-u-s/. https://sciencebasedmedicine.org/are-medical-errors-really-the-third-most-common-cause-of-death-in-the-u-s/. 12. CMS Awards $347 Million to Continue Progress toward a Safer Health Care System.(2016). Centers for Medicare & Medicaid Services. Retrieved October 26, 2016, from https://www.cms.gov/Newsroom/MediaReleaseDatabase/Press-releases/2016-Pressreleases-items/2016-09-29.html. 13. Lyrica. (n.d.). Retrieved April 22, 2017, from www.lyrica.com.

References • Volume 9 • 25

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