The Medical Decoder Winter 2020

TMD

HEALTHCARE MANAGEMENT AND POLICY

Volume 12 The Medical Decoder

IN THIS ISSUE 4 The State of Patient Data and Where It’s Headed Srijit Paul Northwestern ’20

6 Throwing Money at the Problem: How Private Philanthropy and iNGO’s Miss the Mark on Improving Global Health Rushmin Khazanchi Northwestern ’22

9 The Reason (or Reasons) For the Rising Cost of Prescription Drugs Raviraj Rege Northwestern ’22

12 Melatonin Mythbusting Trisha Kaundinya and Troy Biermann Northwestern ’21 & ‘20

EDITORS-IN-CHIEF Troy Biermann Trisha Kaundinya

CREATIVE DIRECTOR Kenneth Wang

EDITING DIRECTOR Raviraj Rege

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LETTER FROM THE EDITOR

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

We’ve decided that, moving forward, we would dedicate each new issue of The Medical Decoder towards a certain topic related to healthcare and medicine. What more relevant topic would there be in the modern political climate than healthcare policy?

We bring you a set of wellwritten and well-researched articles, and we hope that, in reading this edition, you learn something new, become more well-informed on relevant healthcare issues, and gain a better appreciation healthcare management and policy as a whole!

Enjoy!

Sincerely, Trisha Kaundinya and Troy Biermann

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THE STATE OF

PATIENT DATA AND WHERE IT’S HEADED

By Srijit Paul Health care data presents unique challenges and life saving insights. With the advent of big data and its application in practically every industry, it was only a moment of time before the focus shifted towards healthcare. Technology has the potential to improve the health care experience for patients and ease the strain on physicians.

Health care data comprises a broad range of information that is going to reach 25,000 petabytes by next year.1 This is an astounding amount of data, to put this into perspective, health care data is expected to be about 3 billion times the size of an 8 gigabyte flash drive by 2020. To add to this need for better health care data management, the advent of precision medicine has created a demand for better technological tools that require easy data analysis and secure data sharing that can allow for faster specific treatments.2 These mighty technical challenges require innovative solutions that need to overcome a plethora of challenges outside of the technical realm This topic of health care data is often subject to great debate largely due to its sensitive nature. A lot of the debate is surrounded around the Health Insurance Portability and Accountability Act (HIPAA), which was passed into law in 1996 and made personal health data confidential and secure.3 The largest technological step in the field of medicine has arguably been the implementation of electronic health records, which have made patient data digital as well as saving health care workers time.4 However, electronic health records have largely been disliked by physicians due to the large amount of structured data input, requiring many to waste time checking unnecessary boxes.5 In addition to this general dislike for electronic health records, there has been some concern for security. In 2018, there were half a million healthcare records breached. The breaches ranged from billing data to health provider files.6 These general issues in data security does raise questions on the progression towards more accessible data.7

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Another shortcoming of current healthcare data management is the struggle of patients getting access to their own data. Many healthcare providers charge fees or utilize prohibitive channels to bar patients from seeing their own data. These general inefficiencies in the health care data environment showcase the challenging issues that dominate innovation.

Health care data comprises a broad range of information that is going to reach 25,000 petabytes by next year. This is an astounding amount of data, to put this into perspective, health care data is expected to be about 3 billion times the size of an 8 gigabyte flash drive by 2020.

Health care data and its accompanying privacy laws have been in the news quite a bit with the involvement of big dataoriented companies. Google has been collecting patient data on millions of people without notice for a variety of activities. This is a concern due to fears of Google using private data for advertising as well as liking health care data to location and other personal data, further increasing knowledge into personal lives.8 It did not help that Google was set to release 100,000 chest x-rays for public viewing as a way to show off Google’s cloud storage, until the National Institute of Health noted that these X-Rays could potentially expose patient data.9 This comes in the wake of Amazon announcing a partnership with Deloitte to create a better healthcare data sharing system.10 Overall, these large companies may provide greater technological advancements of healthcare data. However, these privacy concerns are not arbitrary distractions.

All these shifting views within the word of healthcare data make the development of new technologies difficult. Privacy and security of the patient is paramount within the healthcare industry.

Tech companies and other innovative entrepreneurs need to be aware of this stance and take this into account when developing new technologies that address the new requirements of modern medicine. Hopefully, there is greater trust and more effort put into secure and easily accessible data within the healthcare ecosystem. It will be exciting to see what the future holds in this burgeoning corner of the healthcare industry.

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Throwing Money at the Problem: How Private Philanthropy and iNGO’s Miss the Mark on Improving Global Health

By Rushmin Khazanchi

No individual quite defines a generation like Bill Gates. A businessman, tech innovator, and visionary, Bill Gates continues to make headlines not for his work at Microsoft, but rather for his role in the Bill and Melinda Gates Foundation, the largest private charity in the world. Gates is one of several prominent social leaders, such as Bill Clinton and Mark Zuckerberg, committed to mobilizing their wealth in the service of the greater good.

Over the years, many of the initiatives promoted by these private philanthropies, as well as other international non-governmental organizations (iNGOs), have focused on global health. From 1990 to 2007, health development aid increased from $5.6 billion to $21.8 billion in part due to the impact of non-profit foundations.1 Proponents of these organizations assert that the vastness of their financial resources, as well as their ability to bypass bureaucratic hurdles, make philanthropies and other iNGOs effective agents in developing a fundamental right to health in developing nations.2 So what’s the issue with such organizations?

The main problem stems from the mechanism used to create impact. When Gates works to eradicate malaria or HIV, he is practicing “vertical intervention.” Vertical intervention occurs when “the solution of a given health problem [is addressed] through the application of specific measures through single-purpose machinery”.3 While great on paper, vertical interventions by iNGOs often fail to create sustainable systems of health delivery in developing nations that are critical to making health access real.

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(In health policy terminology, initiatives that improve the subsystems for health delivery and general population health are known as “horizontal interventions”).

A 2008 analysis of vertical programs focused on HIV/AIDS, malaria, and tuberculosis illustrates that the amount of funding going into these programs is not producing a proportionate impact on patient populations. Over the last few decades, there has been a dramatic increase in funding for TB control in specifically low-income nations. However, despite this increase, only 27% of “active pulmonary TB patients” could access the additional resources of the treatment strategy in 2008.4 Furthermore, the separate, unintegrated treatment channels that vertical programs create confuse hospital workers and foster dissatisfaction due to unequal wage and status levels (perhaps even contributing to the emigration of medical professionals from developing nations).4

When Gates works to eradicate malaria or HIV, he is practicing “vertical intervention.”

Vertical intervention occurs when “the solution of a given health problem [is addressed] through the application of specific measures through single-purpose machinery”.

In that sense, while vertical programs have the ability to divert massive amounts of resources to a single cause, a lack of baselevel infrastructure limits the efficacy of these regimens. In fact, a 2008 analysis showed that a “full implementation” of primary care, with an “integrated clinical setting” to treat diseases that vertical programming often targets, could have prevented 63% of child deaths in the 42 countries that accounted for the vast majority of child deaths.5 Additionally, vertical programs implemented by iNGOs fail to correct the compounding health factors that affect populations in developing nations. Looking specifically to AIDS treatment in Mozambique, the dissonance between creating solutions for a specific problem (in this case, retroviruses) and tangibly improving public health is evident. Statistically, antiretroviral treatment has increased 1500% in the region since it was made widely available due to the work of iNGOs.

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However, once antiretroviral therapy begins and the immune response of patients subsides, the recovery process reportedly unmasks a deep “hunger” masked by the retrovirus, one of the most prevalent “side effects” of the therapy . Due to the lack of resources in the region, many suffered dire health consequences from this “new variant famine”.6 Improving population health in these nations requires a complete understanding of all factors involved, and vertical, disease specific initiatives fail to make significant impacts.

Why, then, do vertical interventions continue to prevail? On a base level, vertical programs are the preferred course of action for many iNGOs because of the ease through which outcomes can be quantified. Per an article in The Lancet: “it is far simpler to demonstrate a 20% improvement in one disease than a 2% amelioration on ten different fronts”.7 The distribution of iNGO funding paints a clearer picture. An analysis of the Gates Foundation shows that 37% of grant funding was allocated to research between 1998 and 2007, with annual funding proportions steadily increasing from 1999 to 2007. However, annual funding percentages for health care delivery systems decreased from 2000 to 2007.8

Solving the aforementioned issues requires a fundamental paradigm shift in how iNGOs operate — a shift from primarily “vertical” interventions to well-balanced “diagonal” interventions for “disease-specific results but through improved health systems”.9 Given how significant iNGO assets are, perhaps the only way to achieve this is to broaden the decision-making process. As the Georgetown Public Policy Institute’s Pablo Eisenberg stated: “[F]oundations with assets larger than almost 70 percent of the world’s nations [are] making decisions about public policy and public priorities without any public discussion or political process".10 Perhaps these organizations could push the funding through public pathways, or increase the influence of physicians or public health officials in dictating where funding goes.

Regardless of the exact solution, one thing is for certain.

Without acknowledging the importance of healthcare delivery and compounding population dynamics in the equation for health rights, a universal standard for global health will always remain an elusive pipe dream.

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THE REASON (OR REASONS) FOR THE

RISING COST OF PRESCRIPTION DRUGS

By Raviraj Rege The rising cost of prescription drugs has been a major issue for individuals and families across the United States. Nearly 7 in 10 Americans currently take prescription drugs on a monthly basis1, and they rely on these medications to maintain better health. Nonetheless, pharmaceutical companies have – especially in recent years – taken advantage of this high demand, using patients’ large reliance on these drugs for their own monetary benefit.

Already, over three dozen drug manufacturers have raised prices of hundreds of medications this year by an average of 6.3 percent2. These growing prices will only prove to be an increasingly significant obstacle for the millions who rely heavily on prescription drugs.

One of the more infamous cases of hiking prescription drug prices was that of Turing Pharmaceuticals, formerly led by Martin Shkreli. Known as the “most hated man in America,” Shkreli raised the price of the antiparasitic drug Daraprim from $13.50/pill to $750/pill after obtaining the manufacturing license. Daraprim has been used to remedy potential parasitic infection, especially in individuals with HIV, and Shkreli justified the rise in price as the only way to make manufacturing of the drug “more profitable” for the company. Despite the outrage caused by the extreme escalation of the drug’s price, the price of Daraprim to this day remains at $750 per pill3. These kinds of price hikes, under current American law, are not considered illegal.

Another significant – and potentially more problematic – example of drug price hiking is that of insulin.

A new CDC report shows that nearly 1 in 3 Americans4 are diabetic or pre-diabetic, and many of these individuals rely on insulin to nearly a daily basis.

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Diabetes occurs when either the pancreas does not produce enough insulin and must be obtained externally or when the body does not use the insulin it naturally produces correctly. From the 2012 to 2016 fiscal years alone, insulin prices doubled5 and have grown even faster in the time since. Some individuals now resort to extremes measures to spend less on insulin, such as purchasing insulin from countries like Canada or Taiwan at a much cheaper price, or – more problematically – by rationing doses of insulin over an extended period of time.. This act of rationing insulin itself resulted in the deaths of three Americans in 20186.

Pharmaceutical companies have – especially in recent years – taken advantage of this high demand, using patients’ large reliance on these drugs for their own monetary benefit.

What is particularly peculiar is how the same medication in the same dosage produced by the same manufacturing company is much cheaper in other countries than in the United States. One major reason for this phenomenon is the concept of drug patents. Three major companies – Eli Lilly, Sanofi Aventis, and Novo Nordisk – own the majority of insulin patents in the United States, and new drug patents can be filed so long as the quality of the drug is not worsened but the exact composition is altered to “justify the increase in price.” In addition, the United States does not ban drug pricing caps, unlike many other developed countries such as Canada, the United Kingdom, and Germany. As a result, the three major companies hike prices much more in the United States in order to “maintain profitability.” While these companies admit that the drug pricing is spiraling out of control, they assert that they are not the source of the problem.

The drug manufacturers tend to blame Pharmacy Benefit Managers, or PBMs, for these price increases.

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The three largest PBMs – Express Scripts, CVS Caremark, and OptumRx – have recently merged with large insurance companies. PBMs are often seen by drug manufacturers as “middle-men,” simply profiting off transactions made at pharmacies whenever the patient uses insurance.

The PBMs create formularies7 —lists of preferred drugs— that dictate the drugs that insurers can cover, so they provide quite a bit of leverage for negotiating price. In doing so, the drug companies blame the PBMs for absorbing profits, resulting in the drug companies to raise their prices to remain in the market.

It only makes sense for the government to step in and institute laws to prevent PBMs, drug companies, and insurance companies from continuing the endless cycle of high drug prices. Some potential solutions include the capping drug prices at certain levels or preventing companies from charging prices for drugs higher than those in other countries.

Congress also has the authority to break patents in an emergency, and this threat has forced some pharmaceutical companies to lower their drug prices. Unfortunately, big pharma companies and PBMs spent over 281 million dollars on lobbying last year alone8. While drug manufacturers, insurance companies, PBMs, and politicians continue to publicly point fingers at one another, executives continue to profit off the millions suffering from the rising cost of pharmaceutical drugs. It is clear that unless those in government take the necessary steps to fight the drug companies, insurance companies, and PBMs, prescription drug prices will only continue to soar and threaten the livelihood of millions of individuals in the United States.

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MELATONIN MYTHBUSTERS

By Trisha Kaundinya and Troy Biermann Melatonin has become informally known as a ‘miracle drug’ to alleviate sleep problems, and the data shows: melatonin is currently the most popular over-thecounter sleep aid, and Americans spent over $400 million on melatonin supplements in 2017 alone.1 Melatonin is added to common items such as vitamins, drinks, and even sweets such as chocolate. The labels on popular melatonin supplements claim that the drug can help users fall asleep more quickly, stay asleep longer, reduce stress, and wake up more refreshed. However, at its core, research has failed to establish conclusive benefits from taking melatonin for most individuals.2 How, then, did the melatonin craze emerge, and how does the market around melatonin remain so strong today?

Melatonin is a neurohormone secreted mainly by the pineal gland, a small endocrine gland located in the center of the human brain in between the two halves of the thalamus.3 Its release is coordinated by the suprachiasmatic nucleus in the thalamus. Biologically speaking, melatonin’s main purpose is to regulate the sleep-wake cycle and maintain synchrony of biological clocks. Melatonin levels also fluctuate in a regular, rhythmic manner; much higher levels of melatonin are observed during the nighttime as opposed to the daytime.4 Melatonin was first isolated in 1958 at Yale University by Dr. Aaron Lerner, who observed that the hormone was largely responsible for dictating changes in skin tone among many reptiles and amphibians, and so the majority of early research conducted with melatonin was focused on its effects on skin health and disease.5

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Dr. Richard Wurtman was among the first to investigate how melatonin affects sleep and, in a 1993 study, found that doses of the hormone helped individuals fall asleep within nine minutes in a dark room at midday.6 Although Wurtman warned against self-medicating with the hormone, the promise of melatonin proved enticing for the pharmaceutical industry; because melatonin could be found naturally in some fruits, vegetables, and grains, it could be marketed as a dietary supplement as opposed to a drug7, and so melatonin soon entered the American marketplace. It was touted as a cure-all for all health problems that might be correlated with sleep challenges such as asthma, trigeminal neuralgia, and Parkinson’s disease.

At this time, melatonin was riding a rollercoaster along with several of its dietary supplement counterparts, and federal involvement was necessary to qualify consumption and to protect consumers. The only law guiding the drug industry up until this point was the Federal Food, Drug, and Cosmetic Act of 1938 (FDCA) which did not include supplements. The Dietary Supplement Health and Education Act of 1994 (DSHEA) defined formally dietary supplements,required statements of nutritional support, and informed corporations on federal expectations for ingredient labeling.

Unfortunately, ever since the DSHEA-led modification of the Federal Food, Drug, and Cosmetic Act in 1994, not much has changed. In 2015, the Council for Responsible Nutrition (CRN), a trade association for supplements, recommended that individual melatonin supplement dosages should not contain more than 10 mg per pill.

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Guidelines on bottle labels also started including recommendations to consult healthcare professionals for true sleep difficulties and before use with children. These recommendations stemmed from the fact that synthetic melatonin is currently unregulated by the FDA because it is characterized as a dietary supplement rather than a drug, and thus quality control is minimal, if at all existent.8 For example, the doses specified on the covers of containers might not be accurate. There is also no information regarding side effects or contraindications of ingesting a hormone.9

Although Wurtman warned against selfmedicating with the hormone, the promise of melatonin proved enticing for the pharmaceutical industry; because melatonin could be found naturally in some fruits, vegetables, and grains, it could be marketed as a dietary supplement as opposed to a drug.

According to a nationwide survey from the Center for Disease Control in 2012, approximately 3 million people were using melatonin sleep aids - a number that has unequivocally risen since. What makes this recent boom concerning is the current state of study regarding melatonin.

Studies have shown that timing of melatonin supplements is essential to calibration of the biological clock.10 When a powerful molecule naturally produced by the human body is taken at inappropriate times in hopes of fixing a sleeprelated symptom or discomfort, it is possible that the clock can be further shifted out of sync with an individual’s sleep cycle.11 The number of individuals who take melatonin without fully doing their research can be attributed to the media-- in many cases, the media may sensationalize stories about science. This tendency toward hyperbole misinforms people and also makes them fatigued when inundated with frequent, often contradictory headlines (“Coffee cures sleepiness?” followed by, “Coffee causes dementia?”).

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Unfortunately, more nuanced and accurate headlines (“Slight correlation between coffee and insomnia, further analysis pending�) wouldn’t sell. Claims that seem accurate on cursory glance can convince a tired flight attendant on his 3rd international flight that melatonin is the only cure.12 What does this mean for someone who might currently be considering melatonin? As always, it is important to read the labels and ensure that you do not have any conditions for which it is contraindicated, among them depression and diabetes. Instead of self-diagnosing, consult a sleep medicine team to discuss any insomnia or sleep challenges that functionally impair aspects of daily life, including shift work or frequent flying between time zones.

In these cases, melatonin might be appropriately prescribed and consumed. The doses recommended (1-3 mg) can elevate blood melatonin 1 to 20 times, so do not preemptively overdose yourself--inappropriate utilization can lead to headaches and stomach pain.13 Melatonin may be entirely worth the hype and it has shown in various contexts to regulate sleep patterns.

However, the intricacies of taking it as a supplement and its effects on biomolecular pathways are still not fully understood.14 Consider it as a fourth tier after analyzing light exposure, sleep behaviors, and consultation of a sleep medicine team.

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REFERENCES The State of Patient Data and Where It’s Headed 1.

What Is Healthcare Data Management and Why Is It Important? Evariant. https://www.evariant.com/faq/why-ishealthcare-data-management-important. Accessed November 14, 2019.

2.

Mirnezami R, Nicholson J, Darzi A. Preparing for Precision Medicine. New England Journal of Medicine. 2012;366(6):48991. https://doi.org/10.1056/NEJMp1114866.

3.

Rouse M. What Is HIPAA (Health Insurance Portability and Accountability Act) ?. SearchHealthIT. https://searchhealthit.techtarget.com/definition/HIPAA. Accessed November 14, 2019.

4.

Poissant L, Pereira J, Tamblyn R, Kawasumi Y. The Impact of Electronic Health Records on Time Efficiency of Physicians and Nurses: A Systematic Review. Journal of the American Medical Informatics Association : JAMIA. 2005;12(5):505-16. https://doi.org/10.1197/jamia.M1700.

5.

Belli B. Yale Study: Doctors Give Electronic Health Records an ‘F’. YaleNews. https://news.yale.edu/2019/11/14/yale-studydoctors-give-electronic-health-records-f. Published November 14, 2019. Accessed November 14, 2019.

6.

Largest Healthcare Data Breaches of 2018. HIPAA Journal. https://www.hipaajournal.com/largest-healthcare-databreaches-of-2018/. Published December 27, 2018. Accessed November 14, 2019.

7.

Miliard M. Patients Still Facing Big Obstacles Getting Their Own Health Data. Healthcare IT News. https://www.healthcareitnews.com/news/patients-still-facingbig-obstacles-getting-their-own-health-data. Published November 14, 2019. Accessed November 14, 2019.

8.

Singer N, Wakabayashi D. Google to Store and Analyze Millions of Health Records. The New York Times. https://www.nytimes.com/2019/11/11/business/googleascension-health-data.html. Published November 11, 2019.

Accessed November 16, 2019.

9.

MacMillan D. Google Almost Made 100,000 Chest X-Rays Public — until It Realized Personal Data Could Be Exposed.

The Washington Post. https://www.washingtonpost.com/technology/2019/11/15/googl e-almost-made-chest-x-rays-public-until-it-realized-personaldata-could-be-exposed/. Published November 15, 2019.

Accessed November 16, 2019.

10. Kent J. Amazon, Deloitte Partner to Address Healthcare Data Challenges. HealthITAnalytics. November 14, 2019, https://healthitanalytics.com/news/amazon-deloitte-partner-toaddress-healthcare-data-challenges. Published November 14, 2019. Accessed November 16, 2019.

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REFERENCES Throwing Money at the Problem: How Private Philanthropy and iNGO’s Miss the Mark on Improving Global Health 1.

Who Runs Global Health? The Lancet. 2019;373(9681):2083. https://doi.org/10.1016/S0140-6736(09)61128-4.

2.

Cockerham G, Cockerham W. Health and Globalization. Polity Press; 2010. 119-47.

3.

Atun RA, Bennett S, Duran A. When do vertical (stand-alone) programmes have a place in health systems? Paper presented at the WHO European Ministerial Conference on Health Systems; June, 2008; Tallinn, Estonia. https://www.who.int/management/district/services/WhenDoVertic alProgrammesPlaceHealthSystems.pdf

4.

De Maeseneer J, van Wheel C, Egilman D, Mfenyana K, Kaufman A, Sewankambo N. Strengthening primary care: addressing the disparity between vertical and horizontal investment. The British Journal of General Practice.

2008;58(546):3-4. https://dx.doi.org/10.3399%2Fbjgp08X263721.

5.

Phipps H. Strengthening Health Systems in Low-Income Countries: Is Giving What We Can Missing a Better Strategy for Saving Lives? Giving What We Can. https://www.givingwhatwecan.org/post/2015/07/strengtheninghealth-systems-in-low-income-countries-giving-what-we-canmissing/. Published July 27, 2015.

6.

Kalofonos IA. ‘All I Eat Is ARVs’: The Paradox of AIDS Treatment Interventions in Central Mozambique. Medical Anthropology Quarterly. 2010;24(3):363-380. doi:10.1111/j.15481387.2010.01109.

7.

Cairncross S, Periés H, Cutts F. Vertical Health Programmes.

The Lancet. 1997;349:S20-S21. https://doi.org/10.1016/S01406736(97)90079-9.

8.

McCoy D, Khembavi G, Patel J, Luintel A. The Bill & Melinda Gates Foundation's Grant-Making Programme for Global Health.

The Lancet. 2009;373(9675):1645-1653. https://doi.org/10.1016/S0140-6736(09)60571-7.

9.

Jimenez YB. Vertical vs. Horizontal Approach: The Drawbacks of Each and a Need for a Merging or ‘Diagonal’ Approach. Brown University ANTH 1310 S01: International Health: Anthropological Perspectives. http://blogs.brown.edu/anth-1310s01/2015/10/22/vertical-vs-horizontal-approach-the-drawbacksof-each-and-a-need-for-a-merging-or-diagonal-approach/.

Published October 22, 2015.

10. Belluz J. The Media Loves the Gates Foundation. These Experts Are More Skeptical. Vox. www.vox.com/2015/6/10/8760199/gates-foundation-criticism.

Published June 10, 2015.

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REFERENCES The Reason (or Reasons) For the Rising cost of Prescription Drug Costs Prescription Drug Costs 1.

Nearly 7 in 10 Americans Take Prescription Drugs, Mayo Clinic, Olmsted Medical Center Find. Mayo Clinic News Network. https://newsnetwork.mayoclinic.org/discussion/nearly-7-in-10americans-take-prescription-drugs-mayo-clinic-olmstedmedical-center-find/. Published June 19, 2013.

2.

Paavola A. January's first drug price hikes average 6.3%: 5 notes. Becker’s Hospital Review. https://www.beckershospitalreview.com/pharmacy/january-sfirst-drug-price-hikes-average-6-3-5-notes.html. Published January 2, 2019.

3.

Johnson C. Y. What happened to the $750 pill that catapulted Martin Shkreli to infamy. The Washington Post. https://www.washingtonpost.com/news/wonk/wp/2017/08/01/w hat-happened-to-the-750-pill-that-catapulted-pharma-bromartin-shkreli-toinfamy/?noredirect=on&utm_term=.bdc990e48217. Published August 1, 2017.

4.

New CDC report: More than 100 million Americans have diabetes or prediabetes. Center for Disease Control and Prevention. https://www.cdc.gov/media/releases/2017/p0718diabetes-report.html. Published July 18, 2017.

5.

Keown A. New Report Shows Price of Insulin Doubled From 2012 to 2016. BioSpace. https://www.biospace.com/article/new-report-shows-price-ofinsulin-doubled-from-2012-to-2016/. Published January 23, 2019.

6.

High insulin costs are killing Americans. Right Care Alliance. https://rightcarealliance.org/actions/insulin/ 7.

Wapner J. (2017, July 27). Understanding the hidden villain of Big Pharma: pharmacy benefit managers. Newsweek. https://www.newsweek.com/big-pharma-villain-pbm-569980.

Published July 27, 2017.

8.

Lobbying Spending Database Pharmaceuticals/Health Products, 2018. OpenSecrets Center for Responsive Politics. https://www.opensecrets.org/lobby/indusclient.php?id=H04&ye ar=2018.

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REFERENCES Melatonin Mythbusting 1.

Loria, Kevin. “Does Melatonin Really Help You Sleep?” Consumer Reports, Consumer Reports, Inc., 23 Jan. 2019, www.consumerreports.org/vitamins-supplements/does-melatoninreally-help-you-sleep/.

2.

Brasure M, MacDonald R, Fuchs E, Olson CM, Carlyle M, Diem S, Koffel E, Khawaja IS, Ouellette J, Butler M, Kane RL, Wilt TJ (2015).

"Management of Insomnia Disorder[Internet]". AHRQ Comparative Effectiveness Reviews. 15 (16): EHC027–EF.

3.

Macchi MM, Bruce JN (2004). "Human pineal physiology and functional significance of melatonin". Frontiers in Neuroendocrinology. 25 (3–4): 177–95.

4.

Gooley, J. J., Chamberlain, K., Smith, K. A., Khalsa, S. B., Rajaratnam, S. M., Van Reen, E., … Lockley, S. W. (2011). Exposure to room light before bedtime suppresses melatonin onset and shortens melatonin duration in humans. The Journal of clinical endocrinology and metabolism, 96(3), E463–E472.

5.

Lerner AB, Case JD, Takahashi Y (July 1960). "Isolation of melatonin and 5-methoxyindole-3-acetic acid from bovine pineal glands". J. Biol.

Chem. 235: 1992–97.

6.

Dollins, A. B., Zhdanova, I. V., Wurtman, R. J., Lynch, H. J., & Deng, M. H. (1994). Effect of inducing nocturnal serum melatonin concentrations in daytime on sleep, mood, body temperature, and performance.

Proceedings of the National Academy of Sciences of the United States of America, 91(5), 1824–1828.

7.

Dietary Supplement Health and Education Act of 1994, Chapter I. Commission on Dietary Supplement Labels.

8.

Erland LA, Saxena PK. Melatonin Natural Health Products and Supplements: Presence of Serotonin and Significant Variability of Melatonin Content. J Clin Sleep Med. 2017;13(2):275-281.

9.

Hitti M. Best Time to Take Melatonin. 2006; https://www.webmd.com/sleep-disorders/news/20060503/best-time-totake-melatonin#1.

10.

Pediatrics AAo. Melatonin. https://www.aap.org/en-us/professionalresources/Psychopharmacology/Pages/Melatonin.aspx.

11.

Davenport L. Melatonin 'Should Be a Last Resort' in Tackling Sleep Issues. 2018; https://www.medscape.com/viewarticle/906835.

12.

CRN Issues New Recommended Guidelines for Melatonin Supplements with Focus on Marketing, Formulation for Sleep Support. https://www.crnusa.org/newsroom/crn-issues-new-recommendedguidelines-melatonin-supplements-focus-marketing-formulation.

13.

Melatonin for Sleep:Does it work? https://www.hopkinsmedicine.org/health/wellness-andprevention/melatonin-for-sleep-does-it-work.

14.

Brody JE. Experimental Evidence Is Lacking for Melatonin as Cure-All. New York Times. 1995, 1995.

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