PULSE VOLUME 6, ISSUE 3. SPRING 2020.
COVID-19 CONCERNS FROM INDIVIDUALS TO THE GLOBAL COMMUNITY
from the editor-in-chief Dear reader,
The past few months have been met with many challenges: from leaders of major countries declaring national emergencies to universities making swift administrative decisions to switch to remote learning. It is not an overstatement to say that all facets of society have been greatly impacted by the novel virus. Nevertheless, our community and people from various parts of the world continue to combat the global pandemic alongside healthcare professionals and teams of researchers endeavoring to mediate the number of cases. In this issue, we discuss some important economic effects of COVID-19 and raise concerns pertaining to our current healthcare system. We are also featuring mental health concerns arisen from behavioral changes due to quarantine and social distancing habits. In research and current events, we introduce developments of new viruses as a tool for cancer treatment, race for COVID19 vaccines, and consideration for street drugs as mental illness symptom treatment method. In these difficult times, we remind everyone to stay connected through various social media outlets, and we encourage our readers to follow up with the most recent guidelines from the CDC and other notable institutions. To this end, we hope that our issue will provide everyone with an opportunity to learn more about current times and become a support needed for continued efforts in overcoming these challenges. Despite the uncertainty surrounding the prospects for our following academic year, whether classes will resume on campus or if remote learning will continue, we hope that you enjoy the read and that you are able to spend a safe and productive summer! With Warm Regards, Linus Park
editors
writers
production
Swathi Balaji EJ Beck Allison Gentry Yifan Mao Shehzaib Raees Adam Rizk
Anna Argulian Sophia Cao Meagan Johnson Miles Kaufman Areeha Khalid Maha Khan
Irena Feng Linus Park
other contributors
Guest Editors: Dr. Brian Callender Professor MK Czerwiec
graphics medicine
MCAT-prep.com Kaplan Test Prep The Princeton Review
pulse - spring 2020
Swathi Balaji Linus Park Adam Rizk
CONTENTS EDUCATION MCAT SHORTENED EXAM & CREATING YOUR MCAT PREP TIMELINE A GUIDE TO TAKING MCAT PRACTICE TESTS KAPLAN MCAT PRACTICE PROBLEM
2 4 5
POLICY THE ECONOMICS OF FLATTENING THE CURVE
6
RESEARCH THE RACE FOR A COVID-19 VACCINE THE "'GOOD" VIRUS RIDING THE REDDIT WAVE
9 12 14
CLINIC MENTAL HEALTH IN THE AGE OF COVID-19 DECIDING HOW TO DIE
18 22
GRAPHICS MEDICINE SOLACE AT LAST
24
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MCAT SHORTENED EXAM & CREATING YOUR MCAT PREP TIMELINE The novel coronavirus has caused tremendous disruption to daily life, including preparing for standardized tests and applying to schools. During this crisis, The Princeton Review has made sure to prioritize the health and safety of our students, teachers, and families. We sincerely hope you are healthy and safe as you read this. As you might know, AAMC has announced that a shortened form of the MCAT will be administered from May 29th through September 28th. This is being done to accommodate the larger-thanusual number of students who will need to take the MCAT late this year—and to facilitate social distancing for examinees. Here is the information you need to know for the remaining 2020 test dates: • There will be three MCAT administrations per test date (6:30 a.m., 12:15 p.m., and 6:00 p.m.; times may vary by location). • Your day will be shorter, but test on the same MCAT content in the same MCAT format. • All sections will have 48 questions per section vs. the standard 59 for Science and 53 for CARS. • Science sections will be 76 minutes. • CARS section will be 81 minutes. • Three 10-minute breaks vs. the standard two 10-minute breaks and one 30-minute break. • Test scoring will NOT change.
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WHAT DOES THIS MEAN FOR YOU?
First, it means you can be more confident that you will be able to take the MCAT this year, so that’s great news! To get prepped for the new MCAT timeframe, practice taking tests with the reduced break; you can do this on The Princeton Review’s online tests by ending the break after 10 minutes.
EDUCATION
COUNTDOWN TO MCAT
Prepping for the MCAT involves some serious planning. Here’s what you need to know about how and when to study right up to test day. When is the best time to take the MCAT? The earlier you sit for the MCAT, the better off you'll be. The field of applicants grows more crowded as the admissions season advances. Even if you complete everything else for your application early, most medical schools will not closely consider your candidacy until they have a copy of your MCAT scores. If you take the MCAT the spring of your junior year (once you have completed your pre-reqs), you’ll have time to retake the MCAT in the summer or following fall, if necessary. How long should I study for the MCAT? Believe it or not, most students who do well on the MCAT spend between 200 and 300 hours preparing for the exam. When you start your prep will be determined by your test date and by what other work and academic commitments you have—usually 3 to 6 months before your exam. View upcoming MCAT test dates, so you can start making a study schedule.
HOW TO STUDY FOR THE MCAT IN THREE MONTHS
If you have three months, here are your MCAT priorities: • Gauge your performance by taking a free online practice test. This first practice test will key you into your strengths and weaknesses and help you determine your baseline score. Now, we offer 2020 Shortened Free Practice Test! • Let your baseline guide your content review. Focus on the sections, topics, or question types you need help with the most before moving on to comprehensive prep. For example, you may decide to start with any subjects not covered by your pre-req courses. • Grab a copy of the AAMC outline of topics that will be on the exam. While textbooks and notes from your pre-req courses can be great resources for reviewing material, you may get tired playing hide-and-seek to find the topics AAMC cares about. Investing in an MCAT prep book, which streamlines the need-to-know information in one place, will save you some time. • Consider taking a prep course to keep you on track. Plenty of MCAT test takers do study on their own, but it doesn’t hurt to review with experts who know the exam inside and out. Choose a course that works with your schedule and goals. If you’re prepping while going to school and also working in a lab, online test prep that’s flexible and convenient could be your best bet. • Practice, practice, practice. Practice questions and tests will show you where the holes in your knowledge are. When you miss questions, try to determine why. If it’s due to being shaky on the material, you need more review on that topic. Make sure you simulate the conditions of the actual MCAT for some of your practice tests.
MCAT 515+ LIVEONLINE SUMMER IMMERSION PROGRAM Make this summer count by achieving your MCAT score goals. Our MCAT Summer Immersion programs are perfect for maximizing your score with focused prep experience. To learn more, visit PrincetonReview.com or call us at 312-379-5893
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A GUIDE TO TAKING MCAT PRACTICE TESTS MCAT practice tests are the best practice you can get when it comes to the MCAT. Two months before your test date, start taking 2 to 3 practice tests per week. Get the most out of each practice test with these tips:
1.
2.
3.
STUDY FOR THE PRACTICE TEST.
For each practice test, set a small goal for yourself such as improving your score in one section by one point or changing your answers on fewer questions thereby minimizing what is commonly referred to as "second-guessing." If you study daily in a manner to achieve these small goals for each practice test, you will ultimately be improving your test-taking strategies and overall performance at the same time.
TAKE PRACTICE TESTS SYSTEMATICALLY.
Similar to the examinations you will have throughout your medical career, the MCAT tests your stamina more than anything else. Therefore, it would be wise to take easier practice tests early on and progress into more difficult practice tests leading up to your test date. Doing this weekly will train your brain to quickly enter a higher functioning state for optimal performance.
REVIEW YOUR PRACTICE TESTS.
Your post-exam review is where your "true gold" lies. Reviewing your practice test not only shows you which questions you missed but also why you missed those questions. Did you just not remember the material? Did you have to guess? Did you forget an equation? Did you misread the question? Did you read all the answer choices? Did you change your answer? Did you run out of time?
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4. LEARN AND IMPROVE FROM EACH PRACTICE TEST.
Make MCAT notes. As you think about each question above, go a step further by writing your thoughts down along with key information from the explanations for questions you missed or guessed on. If the explanations are still not clear to you, research the answers and write out how that answer makes sense to you along with any method you can use to arrive at the answer faster.
5.
MONITOR YOUR PERFORMANCE AND RECALIBRATE AS NECESSARY..
Should you notice a drop in your scores despite your best study efforts, it may serve as an indicator of burnout. You likely need to take a week off from practice tests altogether or at least reduce the number of weekly practice tests you are taking. On the other hand, if your scores plateau, consider that as a signal to tweak your study routine or techniques. Before each practice test, you may also find it helpful to review our convenient science summaries at MCAT-prep.com.
EDUCATION
Kaplan MCAT PRACTICE PROBLEM QUESTION An alpha helix is most likely to be held together by:
A. disulfide bonds. B. hydrophobic effects. C. hydrogen bonds. D. ion attractions between side chains.
THINK YOU’RE READY FOR TEST DAY? Find out with this fun and FREE way to tackle practice MCAT questions from Kaplan Test Prep. Register to receive one sample question a day for the next three months. You’ll get: • A new MCAT-style question each day to test your knowledge and skills • Complete explanations and expert strategies with every question • Compete against your friends to see who’s really ready for test day To get started go to: https://www.kaptest.com/mcat/mcat-practice/free-mcat-practice-question-a-day
C. The alpha helix is held together primarily by hydrogen bonds between the carboxyl groups and amino groups of amino acids. Disulfide bridges, choice (A), and hydrophobic effects, choice (B), are primarily involved in tertiary structures, not secondary. Even if they were charged, the side chains of amino acids are too far apart to participate in strong interactions in secondary structure.
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THE ECONOMICS OF FLATTENING THE CURVE By
MAHA KHAN YIFAN MAO
“Flatten the curve.” This was the most widely emphasized message to the general public in mid-March before the peak of COVID-19 in the United States. The importance of flattening the curve is apparent when evaluating the capacity of the healthcare system in relation to the U.S. population. It is equally important to consider the economic reasons underlying the regulations that have led to this specific capacity level. The need to promote this message became clear throughout March as early estimates showed that about 4 million Americans would be infected by May 13. Given that there are 2.8 hospital beds per 1,000 Americans, it was obvious that there were not nearly enough physical beds let alone supplies and medical workers to care for the number of Americans projected to be hospi-
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talized from COVID-19 given data from China and Italy. The frightening discrepancy between the estimated number of Americans being infected and the capacity of the U.S. healthcare system drove public health officials to begin emphasizing the need to “flatten the curve” and follow social distancing guidelines. Although these measures are not expected to ensure that the U.S. healthcare system will be able to handle all COVID-19 cases, the effort will surely help reduce the amount of serious cases that are turned away or the rationing of medical resources between dying patients. The intersection of basic economics and the healthcare system is not usually discussed in news about the state of the U.S.’s “broken” healthcare system. However, just as in the financial
markets, there are certain key players and incentives to keep in mind when trying to understand the effects of the COVID-19 pandemic on the healthcare system. First, the healthcare system comprises 11% of the U.S.’s labor force, and spending on the healthcare sector makes up 24% of total government spending. Consumers in the healthcare system are patients, who reportedly spend 8.1% of consumer expenditures on healthcare, while the firms are hospitals, private practices, and payors. Although these economic actors play roles of different magnitudes in contributing to the capacity of the healthcare system, the most obvious predicted effect of COVID-19 on the healthcare system was the shortage of hospital beds. This shortage was directly caused by how our healthcare
POLICY
system has been regulated and shaped from its core. Before the onset of COVID-19, rural hospitals in America were already financially strained. A February 2019 report by Guidehouse of 430 hospitals in 43 states found that one in five rural hospitals was at high risk of closing; a number of hospitals that represented 21,547 staffed beds. The possible effects of these hospitals closing down before the outbreak or during would include widening healthcare disparities and decreasing healthcare access, especially in rural areas where there are already fewer hospitals and resources. The contrast between hospitals in rural and urban areas is quite stark considering that NYC’s hospital system has 26,000 beds, which is approximately the same number of beds at all of these at-financial
risk rural hospitals combined. However, the projected rapid spread of COVID-19 in densely populated cities would still keep NYC underprepared for the outbreak. The important question is why healthcare systems in both rural and urban areas are less than prepared to handle pandemics. One of the main drivers of the discrepancy in U.S. hospital beds in comparison to the population is lack of adequate federal regulations and oversight of hospital mergers and acquisitions. In the past decade alone, there have been over 680 hospital mergers. Numerous hospitals have been closed down in various communities nationwide, likely increasing the distance and costs associated with receiving medical care for many people who now do not live in close range to a hospital. The
Federal Trade Commission has not opposed any of these mergers because of a rule that allows hospitals to merge without challenge if one of the hospitals has less than 100 beds. This lack of oversight allows the healthcare system to be controlled by business interests rather than what is best for health equity in society. State-level regulations have also dramatically affected the development of new hospitals to expand the system’s capacity. Specifically, Certificate of Need (CON) laws require a state agency to oversee and approve any major capital spending related to healthcare facilities. These laws prevent more hospitals from opening up because they are based on the economic assumption that an increase in hospital beds will cause healthcare price inflation. They have also
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Source: Guidehouse Report
contributed to extreme hospital bed shortages in some states, but many governors took action to prevent these laws from slowing down the COVID-19 response. 13 out of 35 states with CON legislation suspended the laws via executive orders, while six states expedited the process associated with CON laws. Suspension of these laws has allowed places like NYC to expand their healthcare system capacity and make temporary ICU units in convention centers and nursing homes. Although America’s free market capitalist system drives its healthcare capacity to a size where demand equals supply rather than a size fit to handle a
surge in demand, it is important to understand the tradeoffs with this system. The inflexible, physical constraints of the healthcare system make it clear that the most effective way to lessen the devastating effects of the pandemic and to ensure that the healthcare system is not overwhelmed is by adhering to social distancing measures. Nevertheless, the pressure of the pandemic on the healthcare system capacity has made it clear that the system cannot be reformed without tackling the economic regulations that have enabled healthcare inequities and underpreparedness for the pandemic in America. Barron, Seth. “New York’s Calm Before the Storm?” City Journal, March 20, 2020. https://www. city-journal.org/coronavirus-crisis-nyc-healthcare-system. “CON-Certificate of Need State Laws.” National Conference of State Legislatures, 1 Dec. 2019, www.ncsl.org/research/health/con-certificateof-need-state-laws.aspx.
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Flynn, Andrea, and Ron Knox. “Perspective | We're Short on Hospital Beds Because Washington Let Too Many Hospitals Merge.” The Washington Post, WP Company, 8 Apr. 2020, www. washingtonpost.com/outlook/2020/04/08/ were-short-hospital-beds-because-washingtonlet-too-many-hospitals-merge/. Fournier, Deborah, et al. “Anticipating Hospital Bed Shortages, States Suspend Certificate of Need Programs to Allow Quick Expansions.” The National Academy for State Health Policy, 16 Apr. 2020, nashp.org/anticipating-hospitalbed-shortages-states-suspend-certificate-ofneed-programs-to-allow-quick-expansions/. Meredith, Sam. “Flattening the Coronavirus Curve: What This Means and Why It Matters.” CNBC, CDC Image, 19 Mar. 2020, www.cnbc. com/2020/03/19/coronavirus-what-doesflattening-the-curve-mean-and-why-it-matters. htmel. Mosley, David, and Daniel DeBehnke. “One-inFive U.S. Rural Hospitals at High Risk of Closing.” Advisory, Consulting, Outsourcing Services, Report and Image. Feb. 2019, guidehouse.com/-/media/www/site/insights/ healthcare/2019/navigant-rural-hospitalanalysis-22019.pdf. Nunn, Ryan, et al. “A Dozen Facts about the Economics of the US Health-Care System.” Brookings, 10 Mar. 2020, www.brookings.edu/ research/a-dozen-facts-about-the-economicsof-the-u-s-health-care-system/. Specht, Liz. “Simple Math Offers Alarming Answers about Covid-19, Health Care.” STAT, March 10, 2020. https://www.statnews. com/2020/03/10/simple-math-alarminganswers-covid-19/.
RESEARCH
THE RACE FOR A COVID-19 VACCINE
RESEARCHERS ACROSS THE WORLD ARE RACING TO FIND A CURE
By
SOPHIA CAO SHEHZAIB RAEES
Never had asthma. Never drank alcohol. Never smoked. It didn’t matter. Sammy Schwartz, an ordinary woman living in Brooklyn, became affected by the pandemic that has been affecting everyone worldwide since the beginning of January: the 2019 Coronavirus Disease. Known also as COVID19, over 4.44 million confirmed cases have been announced and
over 302,000 deaths have occurred as of March 14th, 2020. As an overwhelming number of individuals are becoming affected each day, front-line workers and government officials are rushing to save thousands of lives but due to the increasing demand for medical supplies, coronavirus masks, and other necessities, the United States economy is breaking
down. According to a former top US health official Rick Bright, “If we fail to improve our response now, based on science, I fear the pandemic will get worse and be prolonged.” To prevent this from occurring, research companies across the United States as well as the world are racing to find a COVID-19 vaccine.
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the growing prevalence of
COVID-19
Recently, health experts have asserted “that the virus won’t stop spreading until 60% to 70% of the world’s population is immune.” Even according to the World Health Organization, the pandemic was contended to possibly be a disease that might “never go away and the world would have to learn to live with it for good” indicating that COVID-19 might become endemic. Consequently, due to the lockdown actions enacted as a result of the growing presence of COVID-19,
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nearly three million Americans have applied for unemployment benefits reaching an overall 36.5 million mark. The US economy is pummeling down accentuating the necessity of a COVID-19 vaccine and the reopening of the economy. With the United States leading the world with the highest number of COVID-19 cases, the race for the COVID-19 vaccine is in action.
the challenges of finding a cure to COVID-19 With an outbreak beginning in Wuhan, China and soon transitioning into a global pandemic in
less than a few months, COVID-19 proves to be a pandemic that needs to be dealt with quickly through a vaccine. Stated by Dr. Anthony Fauci, the director of the National Institute of Allergy and Infectious Disease, “it might actually require several different vaccines manufactured and distributed by different labs in order to effectively eradicate COVID-19 from the planet.” Currently, 100 vaccines are reported to be under development while seven are presently undergoing clinical trials. In Germany, the CureVac company has proclaimed that an immune response in animals was triggered
RESEARCH
by their experimental coronavirus vaccine. As a result, the first human trials would begin in June through this biotech company. In the US, the pharmaceutical giant Pfizer has begun a COVID-19 vaccine clinical trial with the help of 360 volunteers. On the other hand, there has not been a successful vaccine made yet as scientists across the world scramble to produce an effective COVID-19 vaccination.
the future of COVID-19’s effect on the US Even though a vaccine might turn out to be effective in the near future, the FDA approval process usually takes a year or longer for the vaccine to be approved. According to the top Health and Human Services official Dr. Rick Bright as well, “there’s ‘no plan’ to mass produce and distribute one” and there are “shortages of personal protective equipment.” Based on his input, the earliest a vaccine may be available is early next spring and even so, there are not enough vaccinations that can be produced for the country or even the world. Although Pres-
ident Trump indicated that the military would be mobilized to distribute the vaccine which was proposed to be expected at the end of 2020, the likelihood of this occurring was very low according to health experts including Anthony Fauci. Additionally, due to the controversy between US and China, global tensions are rising over the race for a coronavirus vaccine. On March 13th, two US agencies warned “that Chinese hackers were trying to steal COVID-19 vaccine research” while China countered that the US was “smearing its reputation.” In relation to France, French pharmaceutical drugmaker Sanofi proclaimed that the company would “reserve first shipments of any vaccine it discovered to the United States” angering the French government. As of now, no vaccines have yet been made so each individual needs to take precautions including social distancing to prevent the COVID19 pandemic from spreading even further. Nevertheless, medical researchers across the world are working diligently on producing a vaccine that can save as many lives as possible.
https://www.freep.com/story/news/local/ michigan/2020/05/14/michigan-pediatricmulti-inflammatory-syndrome-covid-19coronavirus-kawasaki-kids/3109695001/ https://www.bbc.com/news/amp/world-uscanada-52657815 https://www.cnet.com/how-to/ coronavirus-vaccine-when-will-we-get-iteverything-we-know-so-far/ https://www.nbcnews.com/politics/congress/ coronavirus-whistleblower-bright-issues-starkvaccine-warning-we-don-t-n1207056 https://news.yahoo.com/curevacs-coronavirusvaccine-candidate-triggered-132526469.html https://www.japantimes.co.jp/news/2020/05/15/ world/global-coronavirus-vaccine-raceheats-up/#.Xr4Wg2hKjZs https://www.bbc.com/news/health-51665497
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THE "GOOD" VIRUS By
ANNA ARGULIAN SWATHI BALAJI
With the onset of the 2020 COVID-19 pandemic, viral research has reached a historical peak. With every university dedicated to unraveling the mechanism behind coronavirus, and every ear attuned to the latest news, the world finally awakened to a long-forgotten and slumbering pathogen: the virus. Although many had forgotten about the versatility of viruses before the pandemic, behind the scenes research rapidly accelerated as modern technology began to cast viruses as vehicles of cancer remedy. Thus, the 21st century saw the rise of the very first “good” virus. Since the early nineteenth century and the advent of cancer treatment, case studies have uncovered the surprising effects of infection in cancer patients. Early reports have shown how coinciding viral infections had the potential to elicit temporary tumor regression and brief remission. A modern example can be seen in a recent Clinical Cancer Research publication, where a strain of the common cold was able to induce
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regression in bladder cancer. With this peculiar correlation, research into virology took a sharp turn in the 1950s but simmered down around the 70s and 80s due to the limiting nature of the approach. At the time, researchers knew too little about the mechanism of tumor shrinkage as well as the possible ways to correctly harness virology to combat cancer. However, with the recent advent of gene editing and further studies into the molecular pathways involved in carcinogenesis, a new revolution in viral immunotherapy began. A cancer prognosis is typically dependent on the present tumor microenvironment (TME). The TME can be classified into a “cold” and “hot” phenotype, where “cold” tumors are immune deserts, with minimal immune cell infiltration, and “hot” tumors are recognized by the immune system. Subsequently, the largest challenge of current immono-oncology is either turning a “cold” tumor into an immunologically responsive tumor or activating already present tumor immune cells that
have been previously inhibited by various cancer mechanisms. Thus, the attractiveness of viruses as clinical targets lies in their ability to elicit strong immune responses and bring in cytotoxic T cells to kill the infected tumor cells. Current research has targeted viral entry pathways specific to tumor cells in an effort to localize the therapy and ensure a minimized systemic effect. Furthermore, a majority of oncolytic viruses are genetically engineered to have deletions in their genome to reduce pathogenicity and instead insert various sequences that either increase specificity to the tumor or even function to produce chemotherapeutic toxins within the tumor. The year 2015 saw the very first FDA approved oncolytic virus, Talimogene Laherperepvec (T-VEC), developed by Amgen with the help of physician Igor Puzanov. Injected intratumorally, T-VEV is a modified form of the herpes virus, with two genes specifically removed that function to strengthen the virus against host immunity. The modified and
RESEARCH
weakened form of the herpes virus is able to enter the tumor cell, alert the immune system, and break the cell down, without spreading or inducing other adverse effects. T-VEC also possesses a newly added gene coding for GM-CSF, which enhances immune system activation. T-VEC is prescribed to late stage melanoma patients and has an over 30% response rate, where 30% of patients see either tumor reduction or undergo full remission. Another novel oncolytic virus currently undergoing multiple clinical trials is TG6002, an altered Vaccinia virus, which functions as not only an alert system for the host’s immune system, but also as a vehicle of drug delivery to the tumor site. Coded to express the precursor FCU1 gene in infected tumor cells, an orally administered pro-drug 5-FC matures into 5-FU within the tumor cells. 5-FU is a strong chemotherapeutic agent that although induces positive therapeutic results at the site of the tumor, also induces negative systemic side effects. By only activating the drug in the localized
tumor area, the oncolytic virus functions both to kill tumor cells and deliver an effective synergistic agent: the chemotherapy drug. The mechanism behind the functionality of viruses in the tumor microenvironment is largely unknown. However, hundreds of clinical and bench trials are currently in progress in an attempt to elucidate the molecular pathways affected by viral attack as well as methods of genetically engineering viruses to induce greater tumor specificity and immunological response. In a time where the word “virus” elicits fear and apprehension, it’s important to highlight oncolytic viruses in an effort to remind society how far modern medicine and research has come. Even though the current times are uncertain, it is reassuring to know that not only has society conquered this enemy before, but it has usurped it to fight its battles. We are the virus of the viruses. Soon enough, even coronavirus will do our bidding.
“First Patient Dosed With Transgene's Oncolytic Virus TG6002, Administered by Intrahepatic Artery Infusion in Colorectal Cancer With Liver Metastases.” BioSpace, www.biospace. com/article/releases/first-patient-dosedwith-transgene-s-oncolytic-virus-tg6002administered-by-intrahepatic-artery-infusionin-colorectal-cancer-with-liver-metastases/. Kaufman, Howard L., et al. “Oncolytic Viruses: a New Class of Immunotherapy Drugs.” Nature News, Nature Publishing Group, 1 Sept. 2015, www.nature.com/articles/nrd4663. Kelly, Elizabeth, and Stephen J Russell. “History of Oncolytic Viruses: Genesis to Genetic Engineering.” Molecular Therapy, Cell Press, 14 Dec. 2016, www.sciencedirect.com/science/ article/pii/S1525001616313314. Lawler, Sean E. “Oncolytic Viruses in Cancer Treatment.” JAMA Oncology, American Medical Association, 1 June 2017, jamanetwork.com/journals/jamaoncology/ article-abstract/2536204. Mansfield, David, et al. “Viral Targeting of Non-Muscle Invasive Bladder Cancer and Priming of Anti-Tumour Immunity Following Intravesical Coxsackievirus A21.” Clinical Cancer Research, American Association for Cancer Research, 1 Jan. 2019, clincancerres.aacrjournals.org/content/ early/2019/06/29/1078-0432.CCR-18-4022.
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RIDING THE REDDIT WAVE
THE SELF MEDICATION OF STREET DRUGS TO MEDIATE MENTAL ILLNESS SYMPTOMS
By
MEAGAN JOHNSON ADAM RIZK
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RESEARCH
So, I have an anxiety disorder and a few years ago I had my first experience with MDMA. It was intense, but ultimately great. My anxiety melted away and I was able to feel fully open and a part of the world. I was uncharacteristically at peace with myself and processed some past trauma without any judgement or fear. Only cons were that I couldn’t sleep that night and my jaw ached the next day. Everyone’s different, but my experience was healing. — u/fablekeeper [Reddit] Tolerance is an issue, neurotoxicity is an issue, purity is an issue. I wouldn't recommend it, it won't work how you expect.1 — u/LSDkid269 [Reddit]
With an increasing dependency on antidepressant medications, many who suffer from anxiety or depression disorders have turned to self-medicating with illegal substances, often referred to as “street drugs.” Faced with either taking life-long doses of selective serotonin reuptake inhibitors (SSRIs) or a single-dosage of MDMA, many patients have flooded the internet validating the wonders of the psychedelic. MDMA, also commonly known as Molly or Ecstasy, is a synthetic drug with a chemical structure similar to the stimulant methamphetamine. Other illegal substances are beginning to meet the historically unmet demand for mental health care and rehabilitation. Ketamine for bipolar disorder, MDMA for PTSD, and LSD for anxiety each appear to repair damaged brain circuits— creating new synapses in the brain. Hoping to mediate the symptoms of these common illnesses, research-backed by both the FDA
and Johnson & Johnson have aided the resurgence of discussing these alternative treatments on internet forums such as Reddit. Yet, many are concerned this is simply solving a problem by creating another—marketing potentially dangerous psychoactive substances to those in an altered state-of-mind. Currently, little attention has been paid to how patients could safely obtain these “street drugs” or how patients could monitor their dosage without clinical intervention. From a national survey during 20112014, in a single month 2.7% of persons aged 12 and over, 8.6% of males, and 16.5% of females took antidepressant medication. Thus, investigating the medical qualities of these select “street drugs” is rather salient. In mice, ketamine has been shown to quickly improve the functioning of specific brain circuits involved in emotion processing and mood. Within hours, it appeared to restore faulty
connections between cells in these brain circuits. One possibility is the “synapses are restored spontaneously once the cells in the circuit begin firing in a synchronized fashion.” Yet, researchers also commented: “What we can imagine is that ketamine always has this short-term antidepressant effect, but then if the synaptic changes are not maintained, you will have a relapse.” Although this potential downside has not been fully investigated, pharmacologists are trying to maintain the restoration of these brain circuits. As of March 2019, the Food and Drug Administration approved Spravato, a nasal spray based on ketamine for treatment-resistant depression; which has a high rate of dissociation in its users. Because of these side effects, including difficulty with attention and suicidal thoughts, patients must be monitored by a health care provider for a minimum of two-hours after the initial dose. According to the FDA, patients in stable remission and
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continued treatment with Spravato plus an oral antidepressant experienced a significantly longer time to relapse into a depressive or manic state than those on the placebo nasal plus an oral antidepressant. Although this is a revolutionary break in the scientific community, these drugs, along with many others formulated from psychoactive drugs, remain dependent on traditional antidepressants and often struggle with the costs of complying to government regulations. The personal accounts of the thousands willing to self-medicate with psychoactive substances to mediate their mental illnesses have largely culminated on Reddit, the social news aggregate. With relatively lax censorship guidelines, Reddit has become a foreground for discussing the tried and true effects of MDMA, mushrooms, and ketamine. Yet, there are broader ramifications
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to prescribing these “alternative antidepressants” to the mass. Websites like Reddit often leave professional advice out of this medical discussion, leaving the largely misinformed to their own devices. Although this is protected under constitutional free speech, Reddit and some of its subscribers are promoting drugs that have yet to be approved by the Food and Drug Administration (FDA): “MDMA greatly reduces or eliminates anxiety (temporarily, but could also have lasting positive effects). 100-150 mg is a good, safe dosage”, says one contributor. In fact, few have been clinically tried on human patients, albeit those patients likely did not have severe mental health issues as those suicidal or manic are often excluded from these psychological studies. There is no way of measuring the severity of one’s mental illness while using these forums. It might allow those with
short-term, situational anxieties to believe their mental condition is analogous to those who have experienced long-term chemical imbalances. While connecting with many others about the potentially life-changing effects of these “street drugs” may be a therapeutic process in itself, approved drugs with such substances have a particularly limited potency. Again, without professional intervention, forums like Reddit cannot address what the appropriate purity or potency of these substances is safe for regular use. Although some may suggest solving part of this issue lies in the censorship or increased monitoring of Reddit’s forums, these discussions quickly delve into limiting freedom of speech law tightly protected by the U.S. Constitution. By limiting Reddit, internet users and citizens of the technological age would be defining which content is enriching
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and what is problematic. To add insult to injury, self-medication threads also construct a problem for the federal government who are already concerned with the prevalence of drug trafficking into the United States. This potential political nightmare is being amplified by the idea that 1) we are autonomous beings and 2) medical conditions can be potentially remedied by holistic or alternative options. Self-medicating is risky, especially among a population highly susceptible to addictive behaviors. Self-medication relies on the prescriber to be of sound mind to properly dose, which is unlikely within the depressive and/ or suicidal population. Even if antidepressant treatment research suggests distributing “street drugs” is too risky, scientists are actively overcoming the stigma attached to less traditional recreational drugs.
r/Psychonaut - Taking mdma with anxiety? (n.d.). Retrieved April 23, 2020, from https://www. reddit.com/r/Psychonaut/comments/6fphax/ taking_mdma_with_anxiety/ Harris, K. M., & Edlund, M. J. (2005). SelfMedication of Mental Health Problems: New Evidence from a National Survey. Health Services Research, 40(1), 117–134. doi: 10.1111/j.1475-6773.2005.00345.x Products - Data Briefs - Number 283 - August 2017. (2017, August 15). Retrieved from https://www.cdc.gov/nchs/products/databriefs/ db283.htm Hamilton, J. (2019, April 11). Ketamine May Relieve Depression By Repairing Damaged Brain Circuits. Retrieved April 23, 2020, from https://www.npr.org/sections/ health-shots/2019/04/11/712295937/ ketamine-may-relieve-depression-byrepairing-damaged-brain-circuits About SPRAVATO™. (2019, July 24). Retrieved April 23, 2020, from https://www.spravato. com/what-is-spravato Illustration: https://twitter.com/thecarljung/ status/956284959928537088/photo/1
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MENTAL HEALTH IN THE AGE OF COVID-10
HIDDEN EFFECTS OF THE PANDEMIC
By
AREEHA KHALID EJ BECK
As the novel coronavirus, COVID19, is transmitted rapidly around the globe, the physical health of vulnerable populations is naturally foremost on people’s minds. However, the spike in pandemic-related mental health problems—especially for individuals who were already experiencing mental illnesses or substance abuse issues—merits just as much concern. World-wide catastrophes caused by diseases, natural disasters, and economic crises have been historically been associated with increased rates of suicide, depression, and anxiety. Moreover, in the case of the COVID-19 pandemic, the very interventions designed to slow the spread of the virus (social distancing, closure of schools and businesses, etc.) are linked with declining mental health. This contradictory effect is related to a multitude of factors, such as anxiety over the future, financial stress,
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job loss, and isolation, all of which have been linked with poor mental health.
the effects of social isolation Social isolation and loneliness in particular are known to have many negative effects on mental and physical health, especially for groups already vulnerable to mental illness. Older adults, for example, have a high risk for developing depression, which, in this population, often remains misdiagnosed or untreated. Older adults also have a high risk of suicidal ideation or death by suicide, accounting for one in five (9,102 out of 48,344) suicide deaths in 2018, according to the CDC. This high risk of death by suicide is linked to loneliness, grief over losing loved ones, and illnesses associated with aging. During the COVID-19 pandemic, older adults make up one of the
populations most at risk of death from the virus and may have decreased contact with loved ones, which can, in turn, lead to an increase in anxiety and fear about the pandemic, as well as a greater risk for depression. Children and adolescents make up another major population at risk for mental health problems during the pandemic. About 12% of individuals aged 12-17 in the U.S. are believed to have depression and anxiety, and though suicide is the tenth leading cause of death overall in the U.S, it constitutes the second leading cause of death for this age group. As the COVID-19 pandemic causes long-term school closings, the CDC predicts children and adolescents will lose access to key mental health resources and support systems provided by friends and teachers, which may lead to a spike in depression and anxiety.
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Furthermore, the practice of quarantining after potential contact with the virus may also cause negative effects on mental health. Past studies of individuals in quarantine (due to illnesses such as SARS, Ebola, H1N1 influenza, etc.) reveal a strong correlation between quarantine and post-traumatic stress disorder (PTSD), confusion, and anger. These effects may be caused by a number of stressors present during quarantine, including fear of infection, loss of routine, and inadequate information about why the quarantine period is necessary.
Even after the quarantine is over, stressors such as financial insecurity (due to the inability to work while in quarantine) and stigma against those quarantined may still be in effect, stalling or slowing down mental recovery.
a turn towards virtual healthcare During these uncertain times, mental health professionals have been advised to keep in close contact with patients already struggling with mental illnesses that may be worsened by the pandemic. Many psychiatrists
have continued to provide care to patients remotely through telemedicine, where appointments can still occur via secure one-to-one videoconferencing technology. Telemedicine has been available to physicians for almost three decades, but the advent of the COVID-19 pandemic has motivated healthcare professionals to utilize this technology with their patients. Call centers, such as that of the National Alliance on Mental Illness (NAMI), have experienced a drastic increase in volume of callers, as people call to express
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their feelings of depression, anxiety, and loneliness. As the vice president of NAMI in Hillsborough, Florida put it, “The coronavirus isn't causing mental illness, it's causing a mental health challenge that's affecting everyone.� This mental health challenge is only exacerbated by the loss of loved ones to the virus, and the cancellation of events such as weddings, proms, funerals, and graduations. In addition to their free nationwide helpline, local branches of NAMI have begun to combat the mental health crisis by setting up emotional support hotlines and support groups over platforms such as Zoom, which serve to create a sense of community for those who feel alone.
the toll on healthcare workers Unfortunately, the increase in panic, depression, anxiety, and other feelings of distress during the COVID-19 pandemic only serve to increase the strain on primary care workers and the healthcare system overall during the pandemic. As the crisis continues with no clear end in sight, healthcare professionals working on the front lines of the COVID-19 pandemic are also at risk for deteriorating mental
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health. Healthcare professionals treating COVID-19 patients are seeing high volumes of COVID19 patients die from the virus, oftentimes unable to connect these patients with their families due to standard isolation procedures. This leads to acute psychological stress and feelings of helplessness, which can have disastrous effects of mental health. On April 26, Dr. Lorna Breen, an ER doctor from Manhattan, died by suicide. Her father, Dr. Phillip Breen, gave a statement to the New York Times, saying that his daughter did not have a history of mental illness, but was killed by the job she loved as she watched patient after patient die of the virus, sometimes before even being removed from the ambulance and brought into the hospital. Dr. Breen’s heroism during the pandemic will be remembered, and her story raises important questions about how doctors and healthcare workers are coping as they find themselves surrounded by the chaos caused by the novel coronavirus. The psychological stress of healthcare workers is amplified by their inadequate access to personal protective equipment (PPE) such as masks, gloves, and hand sani-
tizer due to worldwide shortages. Furthermore, each COVID-19 patient requires high volumes of PPE, resulting in a constant, often unmet, demand. Without access to fresh PPE, healthcare workers have a high risk of passing the virus from one patient to the next, as well as contracting the virus themselves or passing it onto loved ones at home. It is possible that healthcare workers are being fired or acted against at their jobs for voicing concerns over the lack of safety equipment, as revealed by reports sent to the American Nurses Association (ANA) by alarmed nurses, only adding to feelings of distress.
a reminder to reach out The COVID-19 pandemic poses serious problems for short-term and long-term mental health of all individuals affected, from people self-isolating at home to healthcare workers on the front line. Some mental health facilities and resources are doing their best to respond to this challenge, while others struggle to meet the demand of both new and old patients seeking care. The CDC reminds people to practice coping strategies (such as taking breaks from news stories,
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remembering to connect with others, etc.), reading and sharing accurate information about COVID-19, and reaching out to one’s healthcare provider for assistance if/when needed. If you or someone you know about are feeling overwhelmed with feelings of sadness, depression, or anxiety, call 911; reach out to the Disaster Distress Helpline at 1-800-985-5990, or text TalkWithUs to 66746; or reach out to the National Suicide Prevention Helpline at 1-800-273-8255.
1.
Axelrod, Josh, Samantha Balaban, and Scott Simon. “Isolated And Struggling, Many Seniors Are Turning To Suicide.” NPR. NPR, July 27, 2019. https://www.npr.org/2019/07/27/745017374/isolatedand-struggling-many-seniors-are-turning-to-suicide.
2.
Brooks, Samantha K, Rebecca K Webster, Louise E Smith, Lisa Woodland, Simon Wessely, and Neil Greenberg. “The Psychological Impact of Quarantine and How to Reduce It: Rapid Review of the Evidence.” The Lancet, February 26, 2020. https://www.thelancet.com/journals/lancet/article/ PIIS0140-6736(20)30460-8/fulltext
3.
Fry, Elizabeth. “Call Volume to Crisis Centers Increases as Coronavirus Pandemic Continues.” FOX 13 Tampa Bay. FOX 13 Tampa Bay, April 12, 2020. https://www.fox13news.com/news/call-volumeto-crisis-centers-increases-as-coronavirus-pandemic-continues.
4.
Lieberman, Jeffrey A., and Mark Olfson. “Meeting the Mental Health Challenge of the COVID19 Pandemic.” Psychiatric Times, April 24, 2020. https://www.psychiatrictimes.com/coronavirus/ meeting-mental-health-challenge-covid-19-pandemic.
5.
“Mental Health and Coping During COVID-19.” Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, April 30, 2020. https://www.cdc.gov/coronavirus/2019ncov/daily-life-coping/managing-stress-anxiety.html.
6.
Panchal, Nirmita, Rabah Kamal, Kendal Orgera, Cynthia Cox, Rachel Garfield, Liz Hamel, Cailey Muñana, and Priya Chidambaram. “The Implications of COVID-19 for Mental Health and Substance Use.” The Henry J. Kaiser Family Foundation, April 21, 2020. https://www.kff.org/health-reform/ issue-brief/the-implications-of-covid-19-for-mental-health-and-substance-use/.
7.
Watkins, Ali, Michael Rothfeld, William K Rashbaum, and Brian M Rosenthal. “Top E.R. Doctor Who Treated Virus Patients Dies by Suicide.” The New York Times. The New York Times, April 27, 2020. https://www.nytimes.com/2020/04/27/nyregion/new-york-city-doctor-suicide-coronavirus. html.
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DECIDING HOW TO DIE By
MILES KAUFMAN ALLISON GENTRY
At the end of your life, do you know how you want to die? Do you know if you want extreme measures taken to save your life? What measures would you consider to be extreme? Would you want to die in the hospital or in hospice? These questions are not easy to answer, and they’re definitely not easy to ask—especially to those who are terminally ill. But without asking these questions and making these challenging decisions, many patients receive end of life care they never would have wanted. A patient who is terminally ill is not expected to recover, and the quality of their life until the end can vary greatly and is somewhat unpredictable. Some terminally ill patients may be active for a long time before becoming incapacitated while others will deteriorate very quickly.1 This inevitable infirmity results in many patients becoming too ill to make their own medical decisions before they intended, leaving their care in the hands of loved ones. The emotional toll of watching a loved one die slowly and painfully can be traumatic, as can having the
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choice to refuse treatment on their behalf. That is why an advanced directive—a legal document that sets forth a medical plan in case one is unable to make medical decisions—is so important. Physicians have the opportunity to suggest that terminally ill patients create advanced directives and counsel them through various decisions that follow. It has been shown that when people understand their possible outcomes of their illness, they have less anxiety about their disease.2 Most people agree that living is more than being alive, and that patients should decide what medical care they believe will help them live and which treatments they consider too extreme. Although conversations about death are hard, by asking a patient what tradeoffs they are willing to make and counseling them through these painful choices, a doctor can ensure that end of life care matches that patient’s values, and lower the percentage of people who receive excessive or unwanted medical treatment at the end of their life, a fate which currently befalls 25% of patients.2
For end of life care, there are typically two choices: palliative care and hospice care. Hospice is usually reserved for patients who have less than an expected six months of life left, and the primary focus is on comfort. Hospice care is typically provided in the patient’s home or in an assisted living home. These patients receive medicine to alleviate symptoms and pain, but no treatments are prescribed. With palliative care, on the other hand, comfort care happens alongside curative treatments, which are provided in a hospital. Unless otherwise specified by the patient or their family, palliative care tends to be the default type of treatment for terminally ill patients.3 In these medical settings, much can be done to keep a dying person alive. The development of technology like ventilators and dialysis machines have allowed the global life expectancy to double since the turn of the century.4 These medical advances have also lengthened the lives of the terminally ill, which has also lengthened the process of dying. Sick patients sometimes spend weeks or even
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months in the “pre-active phase of dying,” where patients often stop eating, and become lethargic or increasingly restless.5 All of our lifesaving technology has saved many, but how does one decide when to stop saving a dying person’s life and let them go in peace? The answer is highly contested. Some countries like the Netherlands allow doctors to end the lives of terminally ill patients. In the US, physician assisted death was ruled constitutional by the Supreme Court in 1997 and is legal in 9 states.6 Despite legality, many doctors including Ezekiel J. Emanuel, a prominent oncologist and bioethicist, oppose physician assisted death, because they believe that those patients want to die due to their depression and fear of suffering more so than their actual illness.7 The other 57% of physicians in the U.S. support physician assisted death because they believe that someone who is terminally ill should not be forced to suffer a painful end if they choose otherwise.8 Between 1997 and 2018, 2,817 patients chose to end their life via physician assisted death — a
microscopic percentage of terminally ill patients.9 Given the ethical dispute and inconsistent legality, it comes as no surprise that most patients don’t think of physician assisted death as a feasible option. However, one option that many patients do consider is the choice to refuse treatment. In the case of many terminally ill patients, they are no longer able to make their own medical decisions and that responsibility falls on a family member or a court appointed health care surrogate. Death may be a part of life, but nevertheless facing your own mortality is challenging. Decisions about if or when to refuse medical treatment are hard to make. Given the unpredictable progression of a terminal illness, advanced directives become even more imperative. Given the variety of options available and complexity of these decisions, doctors need to be initiating these discussions with terminally ill patients. By creating advance directives with terminally ill patients, we can ensure that all patients are given end of life care that aligns with their values.
1.
“Definition of Terminal Illness.” Marie Curie Charity, 1 Apr. 2019, www.mariecurie.org. uk/who/terminal-illness-definition.
2.
Kalanithi, Lucy, director. What Makes Life Worth Living in the Face of Death. YouTube, TEDMED, 16 May 2017, www.youtube.com/ watch?v=6VacgRdKqjM.
3.
Center for Hospice Care. Know the Difference -- Hospice vs. Palliative Care. Center for Hospice Care Southeast Connecticut, www.hospicesect.org/hospiceand-palliative-care.
4.
Roser, Max, et al. “Life Expectancy.” Our World in Data, 23 May 2013, ourworldindata. org/life-expectancy.
5.
Signs and Symptoms of Approaching Death. Hospice Patients Alliance, hospicepatients. org/hospic60.html.
6.
“Physician-Assisted Suicide Fast Facts.” CNN, Cable News Network, 1 Aug. 2019, www.cnn.com/2014/11/26/us/physicianassisted-suicide-fast-facts/index.html.
7.
Emanuel, Ezekiel J. “Why I Hope to Die at 75.” The Atlantic, Atlantic Media Company, 16 Apr. 2018, www.theatlantic.com/ magazine/archive/2014/10/why-i-hope-todie-at-75/379329/.
8.
Chamie, Joseph. “Assisted Suicide: Human Right or Homicide?” YaleGlobal Online, Yale University, 9 Aug. 2018, yaleglobal.yale.edu/ content/assisted-suicide-human-right-orhomicide.
9.
ProCon.org. “State-by-State PhysicianAssisted Suicide Statistics - Euthanasia - ProCon.org.” Pros & Cons Of Current Issues, ProCon.org, 28 Jan. 2019, euthanasia. procon.org/state-by-state-physician-assistedsuicide-statistics/.
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GRAPHICS MEDICINE: SOLACE AT LAST By Swathi Balaji
Swathi Balaji is a graduating senior at the University of Chicago, majoring in the Biological Sciences and minoring in Health and Society. Swathi served as President of the Pre-Medical Students Association from Spring 2018 to Spring 2020 and has enjoyed writing and editing in PULSE Magazine for the past four years. She will pursue a career in medicine and aspires to us graphic medicine as a tool to communicate science and be a patient advocate.
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“Solace At Last” is inspired by Kathryn Mannix’s book With the End in Mind: Dying, Death, and Wisdom in an Age of Denial. Sometimes, the denial in healthcare settings causes so much more panic and distress than dying itself. Let’s just talk about it.
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ulse p THE PRE-MEDICAL STUDENTS’ ASSOCIATION the university of chicago FACEBOOK /uchicagopmsa WEBSITE pmsa.uchicago.edu
