Penn Healthcare Review Spring 2021 Issue by WUHC

SPRING 2021

WHARTON UNDERGRADUATE HEALTHCARE CLUB

Penn Heal t hcar e Rev iew

E U S S I M R O F E R E H T tor c o D The Now, 4 E G PA See You Will ally Virtu rishnan K Rohan

sing e s e r d 4 Ad h Vaccin 1 E G PA uity Wit Ineq ation Alloc iphode o Aditi D

care t h t l a 7 He The Nex 1 E G PA ds Over Tren de Deca mesh Ra Rajat

co- edit or s- in- chief s Claudia Hejazi-Garcia Helen Wu Wr it er s Rohan Krishnan Eesha Balar Erin Lee Rajat Ramesh Dhivya Arasappan Aditi Doiphode Savan Patel Leeyu Addisu edit or ial Rohan Krishnan Eesha Balar Erin Lee Rajat Ramesh Dhivya Arasappan Sneha Sebastian Leeyu Addisu Design manager Farhaanah Mohideen design t eam Alyssia Liu Shaan Patel

Dear r eader s, You ?r e pr obabl y sick of h ear in g th at th e past year h as been an ?u n pr eceden ted tim e?. H owever ,we th in k th is cl ich é sayin g is a fittin g descr iptor of ch an ges in th e h eal th car e wor l d. Over th e past year ,th e h eal th car e in du str y h as u n der gon e m ajor ch an ges to fil l in adequ acies exposed by th e pan dem ic. In r ecor d tim e, m u l tipl e COVID-19 vaccin es wer e devel oped an d com m er cial ized. Vir tu al doctor appoin tm en ts h ave, an d pr obabl y wil l , becom e th e n or m . Dispar ities in h eal th ou tcom es for differ en t popu l ation s, su ch as u n der r epr esen ted m in or ities or l ow-in com e in dividu al s, du r in g th e pan dem ic h ave spar k ed a pu sh for equ ity an d ju stice in h eal th car e. Th is year ,we al so l ived th r ou gh th e el ection of a n ew pr esiden t an d pon der ed wh at th is n ew adm in istr ation m igh t br in g to th e fu tu r e of h eal th car e. For in stan ce, wou l d th e Affor dabl e Car e Act be expan ded to in cl u de u n docu m en ted im m igr an ts? W ou l d th e gover n m en t fin al l y h ave a say in th e dr u g pr ices th at ph ar m aceu tical com pan ies set? Th ese ar e al l qu estion s th at we bel ieve th is n ew r efor m wil l give u s an swer s to. As Pen n stu den ts, we?ve per son al l y witn essed Pen n adm in istr ator s h over back an d for th between vir tu al l ear n in g an d h ybr id cl asses. For th is issu e, we wan ted to r efl ect h ow differ en t for ces h ave r espon ded to al l th ese ch an ges an d tr an sfor m ed th e h eal th car e l an dscape. Th u s, we pr esen t to you Th e Refor m Issu e. Th an k s for stick in g with u s th r ou gh th ese th r ee sem ester s of on l in e pu bl ication . W e can ?t wait to h an d ou t a h ar d copy of ou r Review to you in th e Fal l . Best, H el en an d Cl au dia

Please note: These articles were prepared by members of the Wharton Undergraduate Healthcare Club. The opinions do not represent the school or club's official opinions on the issues. The Wharton Undergraduate Healthcare Club is an independent, student-led organization of the Wharton School of the University of Pennsylvania. All content is the responsibility of the club.

cont ent s

4 The Doctor Will See You Now, Vir tually Written by Rohan Krishan | Designed by Alyssia Liu

7 CAR T- Cell Ther apy: A Compar ison of Autologous and Allogenic Modalities Written by Savan Patel | Designed by Farhaanah Mohideen

Dispar ities in Newbor n Health Outcomes

Written by Erin Lee | Designed by Farhaanah Mohideen

12 Penn Through the Pandemic 14 Addressing Inequity with Vaccine Allocation Written by Aditi Doiphode | Designed by Shaan Patel

17 Climate Change: Healthcare's Next Biggest Threat Written by Dhivya Arasappan | Designed by Farhaanah Mohideen

The COVID- 19 Nur sing Shor tage and Its Implications Written by Eesha Balar | Designed by Alyssia Liu

The Future of Alzheimer 's Disease Research

Written by Leeyu Addisu | Designed by Alyssia Liu

24 Healthcare Trends Over the Next Decade 2 Shaan Patel Written by Rajat Ramesh | Designed by 2

THE DOCTOR WILL SEE

W r itten By: Roh an Kr ish n a

More than a year has passed since the coronavirus pandemic engulfed our country in the chaos of nationwide lockdowns, toilet paper shortages, and sourdough starters. The imposition of stay-at-home orders in mid-March sent the medical establishment reeling as almost overnight doctors closed practices and opened laptops to commence virtual care. The Center for Disease Control (CDC) reported a 154% increase in telehealth visits over the final week of March 2020 as compared to the same week a year prior.1 Even as new cases and death rates fluctuate across the U.S., telehealth providers like Amwell have sustained consistent growth attributed to both CDC protocols and patient-provider satisfaction with virtual modes of care.2 W ith vaccination rates climbing, it remains to be seen how telemedicine? having demonstrated its immense potential? will continue to be utilized as we look to the new normal. Before the pandemic, NOVEMBER 2016 telemedicine ISSUE # 2232was viewed as an ancillary service to be used alongside in-person triage and 4

care. Beyond the live video conferencing that is generally associated with telemedicine, store and forward services, or asynchronous telemedicine, have been used for decades by ophthalmology and dermatology practices, where patients and doctors exchange images, MRIs,

"The CDC reported a 154% increase in telehealth visits over the final week of March 2020 as compared to the same week a year prior."

X-rays, and other medical information via secure 3 messaging platforms. However, telemedicine was widely relegated to niche applications in specific specialties, like the transmission of images for dermatology visits, rather than being used across specialties as a primary tool.4 These narrow

applications are a reflection of how telemedicine was covered by health insurance providers. Pre-pandemic, states set their own policies on telemedicine regarding which services were covered, over which geographic regions, and how to reimburse providers.5 Under Medicare guidelines, telehealth services were limited to special care needs for patients in only remote or rural areas, requiring real-time audio and video visits and HIPAA-compliant platforms while patients and doctors were unable to conduct visits from their homes or across state boundaries.6 Even as innovations in video technology soared, regulators moved at a snail?s pace in revamping insurance guidelines to match the potential of these technologies. However, with the widespread cessation of in-person visits in March of 2020, telemedicine was cast into the spotlight as the de facto remedy. The Centers for Medicare and Medicaid Services (CMS) were among those driving the shift in telehealth?s popularity. For the duration of the pandemic, CMS instituted a waiver that reimbursed all office,

YOU NOW, VIRTUALLY

an | Design ed By: Al yssia Liu

hospital, and other telehealth visits by doctors, nurse practitioners, clinical psychologists, and licensed social workers in the same way as in-person visits, while expanding covered services across live telecommunications, store-and-forward technology, and communication via an online patient portal.7 Private payers have followed in CMS?s footsteps, while additional regulations surrounding the use of non-HIPAAcompliant platforms, like FaceTime, and the enforcement of state boundaries for patients and doctors were also waived.8 As regulations on telemedicine were eased at light speed, the barrier for patients to access quality healthcare services was lowered immensely. In reference to rapid shift towards telehealth, Dr. Jules Lipoff, a dermatologist from the University of Pennsylvania, remarked, ?it is either telemedicine or no care at all.?9 In the months since its rapid adoption across healthcare

providers, telemedicine has far exceeded the bar of a mere band-aid solution. Since March, hospital groups and practices across the country sought telehealth partnerships with companies like Teladoc and Amwell or developed proprietary solutions, like Massachusetts General Hospital?s eVisits platform. Even from

specialties. During this period, patient satisfaction with telemedicine surpassed satisfaction with in-person visits, at 94.9% and 92.5% 11 respectively. Of the 1594 healthcare professionals surveyed in the COVID-19 Healthcare Coalition?s Telehealth Impact Study, 77% of respondents held that they could deliver quality care via telehealth.12 Still, notable deficiencies persist in providing treatment via virtual modes of care. Across specific specialties, telemedicine does not suffice for clinical tests and hands-on diagnoses. In a Source: Ramaswamy, Ashwin et al., 2020 specialty-focused study behind a computer screen, from the George W ashington patients and doctors alike have Medical Faculty Associates' remarked on the quality of Dermatology department, about telehealth services, while citing one-quarter of patients cited efficiency, reliability, and ease of concerns of inadequate use amidst other positive assessment and a lack of physical attributes.10 At New touch for reasons they did not York-Presbyterian Hospital, like their telehealth synchronous video visits appointment.13 Although there increased by 8729%from April 1, are specific instances that 2019 to March 31, 2020, used for question telemedicine?s efficacy, 4 over 200 visit types across 40 overall patient-provider 4

"While FaceTime and Zoom offer convenience, the lack of stringent encryption standards poses a serious security risk as providers and patients discuss sensitive medical information online." satisfaction with virtual care provides ample evidence of how telehealth has flourished during the pandemic. Considering telemedicine?s vast success over the past year, we can look to its potential beyond the pandemic to sustain access to quality healthcare services for patients across geographic and socioeconomic strata. On the regulatory side, the benefits of telemedicine can only be sustained if CMS and state governments continue to support telemedicine?s reimbursement parity with in-person visits to ensure that virtual services are a financially viable offering for providers. This past December, CMS announced that more than 60 of the 144 telehealth services offered during the pandemic will continue to be covered with the end of the public health emergency.14 Following suit, New York Governor Andrew Cuomo announced legislation this past January to require Medicaid telehealth reimbursement for services 6

conducted outside of a clinical setting, develop interstate licensing reciprocity for states across the Northeast, and mandate that commercial insurers offer telehealth programs that reimburse at rates that ?incentivize use.?15 But even with these regulatory successes, telemedicine?s notable deficiencies need to be directly addressed for virtual care to be sustainable over the long term. To start, providers need to strike an optimal balance between services that are best offered virtually and those that are more aptly served by in-person consultations. W hile store-and-forward technologies might improve efficiency for

"More than 60 of the 144 telehealth services offered during the pandemic will continue to be covered with the end of the public heath emergency"

non-emergent acne cases, in-person visits for other dermatological conditions that demand full-body examinations can improve diagnostic accuracy and patient satisfaction. On a more specific note, CMS?s relaxation of HIPAA standards for telemedicine platforms needs to be corrected once the pandemic ends. W hile FaceTime

and Zoom offer convenience, the lack of stringent encryption standards poses a serious security risk as providers and patients discuss sensitive medical information online. Finally, policymakers and health systems need to properly allocate resources to improve access for disadvantaged populations and bring telemedicine?s potential to fruition. During the pandemic, telehealth services were utilized far less by patients in impoverished communities, a trend attributed to the ?digital divide? in telemedicine access.16 Innovations in healthcare technology carry far less weight in improving health equity without policy measures to implement these innovations. Initiatives like grants to improve broadband and digital infrastructure in low-income areas will allow telemedicine?s potential to be fully realized. Even as we ascend from the depths of endless takeout dinners and awkward breakout room interactions, virtual modes of care will remain long after we flatten the curve. Through coordinated efforts by healthcare providers and the government, we can ensure that telemedicine continues to improve medical outcomes and make quality healthcare accessible for all.

CAR T-Cel l Th er apy: A Com par ison of Au tol ogou s an d Al l ogen ic M odal ities W RITTEN BY SAVAN PATEL DESIGNED BY FARHAANAH MOHIDEEN

Recent advancements in cell therapy, specifically with chimeric antigen receptor T-cell (CAR T) therapies, have demonstrated that this class of treatments has the potential to drastically improve clinical outcomes for those experiencing hematopoietic disorders ? disorders of the blood. However, the field has become polarized regarding the optimal source of these modified immune cells. Proponents of autologous cell therapies advocate for a method involving the conversion of a patient?s T cells into cancer-targeting cells.1 On the other hand, advocates of allogeneic cell therapy, on the other hand, suggest that transplanting modified versions of a single donor?s T cells is a superior strategy in facilitating patient outcomes.

6 6

AUTOLOGOUS CELL THERAPY After the approval of Novartis Pharmaceuticals? Kymriah in mid-2017, the cell therapy space has been largely dominated by autologous technologies (described below in more detail). Such therapies have now been approved for a variety of hematopoietic disorders including acute lymphoblastic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL).2 The basis for these platforms involves the extraction of naïve lymphocytes from patients, the introduction of ligand-binding proteins (chimeric antigen receptors), and subsequent transplantation into the original patient?s bloodstream. As of March 2021, all four approved CAR T-cell therapies are autologous in their modality (Kymriah, Yescarta, Tecartus, Breyanzi). However, the continued expansion of these therapies masks many of the unsolved supply chain issues that hinder the rapid expansion of these products. Specifically, the processing of T cells from patients requires careful storage and shipment to manufacturer sites where they undergo therapeutic modifications necessary to treat disease. Further complicating the matter, some treatment centers do not have apheresis centers on-site (locations at which the actual blood extraction procedure takes place), elongating processing times and extending the supply chain. The low density of 8

manufacturer cell processing sites also contributes to slow turnaround times. As a result, patients are expected to stay for several days in the vicinity of the treatment center to complete the entire transplantation process.3 As a result of these complex supply chain dynamics, cell therapy products tend to fetch a high price. Fierce Pharma writes, ?The one-time therapy came with a lofty price tag of $375,000 per patient.?4 The costs associated with these therapies are expected to dwindle over time as manufacturers expand cell processing capabilities, treatment centers develop their cell therapy teams, and pricing is pressured by new autologous products and allogeneic platforms. ALLOGENIC CELL THERAPY Allogeneic cell therapies, such as those being developed by Allogene Therapeutics, are aimed at improving many of these industrial supply chain challenges. Specifically, this technology relies on the utilization of modified T cells from a single donor to treat multiple patients. However, no such therapy currently has been approved. The major concern amongst field experts is that allogeneic transplants run the risk of graft vs. host disease (GVHD) ? a condition in which the patient?s immune system rejects a transplant. However, Allogene has recently produced Phase 1 results (safety and efficacy data) on two

allogeneic CAR T cell therapy products for separate indications within the last year. Although much of the Phase 1 data is merely indicative of safety profiles and a few efficacy endpoints, Allogene was able to demonstrate high tolerance of their therapy. Specifically, ALLO-501 (Allogene?s CAR T product for DLBCL) showed in a Phase I study (22 patients) that their product had no cases of GVHD and had a ~37% complete response rate (in line with expected success rates for autologous therapies).5 That being said, future studies on larger patient populations will likely reveal more accurate data on efficacy and safety with these drugs.

being developed to improve delivery to T cells.7 Improved cell product would improve the supply chain issues that both autologous and allogeneic therapies face. FUTURE DIRECTION

Allogeneic therapies can increase patient access to CAR T-cell therapy through its designation as an ?off-the-shelf?treatment. However, there are several drawbacks beyond immunological responses. For example, the expansion of the donor lymphocytes poses an issue for scaling up these manufacturing processes. Moreover, allogeneic CAR T tends to have decreased long-term efficacy and may require supplemental injections to maintain sufficient anti-cancer activity.6 These two factors complicate the manufacturing pipeline and supply chain. CELL THERAPY ADVANCES More broadly, there are also several ongoing innovations in the cell therapy field that will likely enable both of these therapeutic modalities to become more accessible in the next decade. For example, many academic labs are exploring unique methods for preventing transplant rejection and GVHD. For example, one method for minimizing immunological rejection is through the modulation of various cytokines and immune molecules that may contribute to this rejection ? an important consideration for allogeneic transplants.6 Second, cell processing technologies are also being developed. For instance, the chimeric antigen receptors typically introduced to T cells through mRNA-loaded viral vectors or electroporation ? both of which are highly cytotoxic to cells. 8 Novel platforms such as lipid nanoparticles are 8

There are several factors to consider when trying to evaluate whether the future of cell therapy lies with allogeneic or autologous platforms. First and foremost is efficacy. Given the early-stage nature of allogeneic cell therapy clinical trials, it is difficult to compare the two platforms. That being said, factoring in possible transplant rejection, it is not unreasonable to expect that allogeneic therapies will be less effective or as effective as autologous therapies. Second, development timeline. As previously discussed, autologous therapies are dominating the market, at present, with 4 approved autologous CAR T-cell therapies. Several more autologous therapies are in development pipelines at large pharmaceutical companies. As such, these therapies have a significant first-mover advantage. Treatment centers are likely to fully integrate autologous therapies into the standard-of-care in the next few years. W hen an allogeneic therapy is eventually approved, it will have to demonstrate to physicians that its benefits outweigh that of a tried-and-true therapy. Finally, that same time advantage would enable manufacturers to further develop the infrastructure to eliminate many of the supply chain issues that they face. In doing so, they could reduce price and patient time burden, making such therapies more attractive. Regardless of which modality will dominate the market over time, both have and will continue to benefit blood cancer patients through continued innovation and improved clinical outcomes.

DISPARITIES IN NEWBORN HEALTH OUTCOMES WRITTEN BY ERIN LEE DESIGNED BY FARHAANAH MOHIDEEN

One of the most prominent issues that has emerged in the wake of the pandemic are the significant disparities in health outcomes for minorities. In July of 2020, it was reported that 73.7 out of every 100,000 black Americans had died from coronavirus, in comparison to a rate of 32.4 per 100,000 for white Americans.1 This disproportionate rate of COVID deaths in black populations is just one example of the health disparities that minority communities face. In fact, many of these disparities are predetermined by various environmental and socioeconomic factors rooted in structural racism. These health inequalities are almost programmed before birth, during pregnancy. The infant mortality rate of African Americans is 2.3 times more than whites.2 The disparities in newborn health is a crucial indicator of the inherently racist institutions our country is built upon that persistently interfere with maternal healthcare during pregnancy and beyond, resulting in an entirely avoidable loss of human life. 10

Due to practices like redlining, many minorities, particularly the black community, are more likely to be exposed to pollution and other environmental toxins.3 The increased exposure to pollution caused by residential segregation results in lower birth rates (one of the most prominent health indicators for newborns) and increased rates of asthma in black children.4 Not to mention, living near chemical plants exposes expecting mothers to carcinogens that are extremely harmful to their babies. Unfortunately, it is still difficult today for minorities to move from these locations due to persisting housing segregation. Furthermore, minorities also lack the political power to be able to combat these inequities.5 Yet another issue these communities face is food insecurity. Many lower-income neighborhoods that minorities live in do not have access to nutritious and affordable options, and are even encouraged to consume fast food, alcohol, and cigarettes through corrupt marketing tactics.6 This has a direct impact for pregnant women, for whom it is imperative to consume the necessary nutrients to nourish them and their baby. Experiments on pregnant mice have shown that calorie-deficiency can change the gene expression in offspring, making them prone to diabetes.7 Essential nutrients like folate which low-income mothers may be missing from fruits and vegetables can be linked to neural tube defects.9 In addition, poor nutrition can increase the risk of obesity and heart disease.

" THE CULMINATION OF

THESE FACTORS IS THE RESULT OF A STRUCTURALLY RACIST SYSTEM THAT PUTS PREGNANT WOMEN OF COLOR AT RISK. "

The experience of stress and trauma also drastically affects newborn health. Low-income workers face long-term stress of keeping up with bills and providing for their families. Because the body responds to stress by releasing hormones to ignite the fight-or-flight pathway, some hormones such as cortisol can actually contribute to early birthing, resulting in lower birth rate and increased risk of newborn death.9 Interestingly, in a study conducted by two Stanford researchers, Persson and Rossin-Slater, the emotional stress from a death in the family prenatally resulted in higher medication usage for ADHD and depression than a death in the family occurring after birth.10 This demonstrates the great extent to which a combination of factors can contribute to medical issues that a child will face throughout their lifetime, before they are even born. The culmination of these factors is the result of a structurally racist system that puts pregnant women of color at risk because of their location and other socioeconomic barriers that restrict access to proper nutrition and healthcare services. Furthermore, once they 10 10

are using healthcare services, minorities are often reported to receive poorer quality healthcare than white women. 11 Aside from pregnancy itself, many women of color undergo distinct traumatic struggles, the effects of which may be passed onto their children. As previously discussed, prenatal stress can result in lower birth rate and lead to higher rates of mental health issues in children, setting them up for poorer health in comparison to their white peers.12

" BECAUSE THESE

DISPARITIES ARE ROOTED IN RACISM, IT WILL TAKE A LONG TIME TO REVERSE THESE EFFECTS. "

W hile some policies have made significant improvements in equalizing newborn health, some of the programs have lost funding or been under attack by the previous administration. States that haven?t expanded their Medicaid coverage since the Affordable Care Act was imposed are leaving many low-income adults uninsured, creating gaps that were supposed to be filled by Medicaid expansion.13 The SNAP program (Supplemental Nutrition Assistance Program) was also under threat by the Trump Administration, which imposed restrictions that would have caused many to lose their food assistance while making it nearly impossible for others to obtain. 14 There are several arenas to tackle when it comes to disparities in newborn health. Because these disparities are rooted in racism, it will take a long time to reverse these effects. However, increasing funding towards support programs, and creating more environmental and healthcare policies can help. Key areas that must be addressed are improving both quality and access to healthcare, addressing both maternal and infant mental health, building better pre and post-birth support systems, and improving data collection on fetal and newborn health.15 W hile issues of healthcare disparities have been a major focus in healthcare in the midst of a pandemic, we must not forget about these issues once COVID is finally under control. These issues have existed since before the pandemic, and will continue to persist after. W ith the rise of a new presidential administration, we are faced with the task of filling in the gaps, until low income minorities are able to feel confident that their health and the health of their future children will not be at risk solely because of their skin color. We owe it to the future generations of this country to establish an equal opportunity for a healthy and fulfilling future, one that isn?t tampered with long before they are even born.

penn t hr ough t he

epandemic 12

Ad d r essi n g I n Vacci n e Al

WRITTEN BY AD DESIGNED BY

OVID-19 has drastically changed lives contributed to these alarming rates. Racial and worldwide. And many, like myself, are ethnic minorities are more likely to live in eager to return to our lives prior to the congregate settings or work essential jobs, which pandemic. Now, the various COVID-19 puts them at a higher risk of infection. This is vaccines are presented as a beacon of hope to compounded by the fact that unfortunately, the end of this year-long nightmare. As of March these marginalized populations are also less 2021, 82,572,848 doses of the vaccine have been likely to seek medical attention due to lack of 1 administered in the United States alone. Vaccines insurance and mistrust in the healthcare system. usually take 10 to 15 years to be developed and In low income settings, people often lack access authorized. Compared to the measles vaccine, to specialized or quality healthcare which would which was previously developed in a record time improve their chances of survival.4 of 4 years, global research efforts and As states continue to distribute vaccines, some developments have made history health departments are working to reduce the by creating, authorizing, and disparities that have become so distributing a COVID-19 vaccine in apparent during the pandemic by less than one year. W hile the "W h i l e on l y 12% of including these vulnerable vaccine development in itself is a populations at the forefront of their t h e cou n t r y ?s tremendous feat, it will be equally vaccine allocation plans. Each of the important to monitor how the p op u l at i on i s United States? 64 jurisdictions? vaccines are administered. Most including states, major cities, and n on -H i sp an i c importantly, how is the vaccine territories? have the autonomy to being distributed and to whom? Bl ack , n ear l y 34% create their own vaccine allocation First and foremost, it is important to plans to distribute the COVID-19 of COVI D-r el at ed recognize that COVID-19 has vaccine provided by the federal d eat h s w er e disproportionately impacted certain government. Almost all am on g t h i s populations. Low income jurisdictions are implementing a communities have suffered phased approach. The vaccines p op u l at i on ." economically, struggling with will be distributed from Phase 1 to increased debt, housing instability, 4, with Phase 1 including the most and the inability to take time off from vulnerable populations. Each work.2 However, even within these communities , jurisdiction has categorized priority there has been a racial disparity in COVID-19 rates. groups ? populations that will receive the Racial and ethnic minorities, specifically Hispanic, vaccine first.5 Recognizing the disproportionate Latino, non-Hispanic Black, non-Hispanic impact of COVID-19 on ethnic and racial American Indian, and Alaska Native people, have minorities, many states have decided to take experienced higher mortality rates. W hile only these socioeconomic disparities into account 12% of the country?s population is non-Hispanic through allocation and uptake. Black, nearly 34% of COVID-related deaths were ALLOCATION among this population.3 States have largely followed the Longstanding inequities in healthcare have 14

n equ i t y w i t h l l cat i n

DITI DOIPHODE SHAAN PATEL recommendations of National Academies of Sciences, Engineering, and Medicine and CDC?s Advisory Committee on Immunization Practices when determining who to include in each phase of allocation. Generally, almost all jurisdictions include healthcare workers, frontline essential workers, and people with 2 or more comorbidities in Phase 1. However, many states have gone beyond the most obvious at-risk populations to include ethnic and racial minorities in Phase 1 or 2.6 States, like Delaware and Iowa, have explicitly included minority populations in their ?priority population groups identified most at risk.?7

indices implement several different factors, such as geographic area, poverty level, social factors, and race and ethnicity, to determine how vulnerable or deprived a certain area is.8 This area can then be targeted for vaccination efforts. States have indicated different uses for these disadvantage indices - to prioritize worse off, define priority groups, plan outreach, and planning dispensing sites.9 The integration of race and ethnicity into these indices provide states with an indirect way to include vulnerable racial and ethnic populations in especially deprived areas in vaccine allocation.

For instance, the CDC has recommended that these populations be categorized and identified using different indices, some including the Social Vulnerability Index (SVI), Area Deprivation Index (ADI), and Covid Community Vulnerability Index. California has created their own equity metric that they will use to identify these groups. These

UPTAKE Just as important as distributing the vaccine is ensuring that it is being administered effectively. Historical mistreatment, such as the Tuskegee Syphilis study, has led many racial and ethnic minorities to harbor mistrust in the medical system. Beyond research abuse, Black patients are also regularly undertreated for pain compared to their white counterparts.10 A lack of trust between vulnerable populations and the healthcare system underlies the significant rates of vaccine hesitancy. A study has found that 53% of Caucasians plan to receive the vaccine when available, whereas only 24% of African-Americans

14 14

Source: Sinha, Avilasha. 2021. "Reducing COVID-19 vaccine hesitancy among racial and ethnic minorities ." Baylor College of Medicine. January 22.

and 34% of Latinxs plan to do so.11 This creates a dilemma where the populations who are most at risk for COVID-19 are less likely to take a measure that will protect themselves. States have implemented several initiatives to reduce vaccine hesitancy and dispel mistrust targeted at racial and ethnic minorities. North Carolina dedicated an entire appendix to a communications plan for historically marginalized populations and Massachusetts has sponsored grants for communities that can be used to promote outreach. Many states plan to focus messaging on these groups as well. Arkansas?communications will target Hispanic and Marshallese communities in a way that is ?empowering and inspirational while avoiding stigmatization.?12 Many states are also including community leaders in their planning committees and implementing feedback from stakeholders. Emily Sadecki, a Bioethics masters candidate and medical student, conducted a research study evaluating these initiatives. Sadecki emphasizes that the emphasis on ?co-creation? with stakeholders is key to making sure state plans actually address community needs. ?W hile these efforts may not completely erase vaccine hesitancy rooted in historical trauma, I think that they are an important first step in not only understanding the role that racism plays in creating unequal outcomes, but making efforts to address it,?Sadecki says.13 Moreover, the two leading vaccines, Moderna and Pfizer, require two shots for full 16

effectiveness.14 Current methods of administration focus on providing two doses to everyone rather than giving everyone one dose. Patient information is collected to record administration of the first dose and to follow up with the second dose. This presents a problem for undocumented immigrants. Many undocumented immigrants have not actively sought vaccination due to the fear of deportation. W ith this concern in mind, the US Department of Homeland Security and CDC have released statements expressing that ICE operations will not be carried out at vaccination sites and patient information will not be used for immigration enforcement.15,16 However, this is still an important consideration for outreach efforts as many states containing high undocumented populations are focusing their communications on this issue. CONCLUSION State vaccine allocation plans must acknowledge disadvantaged racial and ethnic minorities in their vaccine allocation plans. To maintain social justice and equity, it will be important to monitor how states are implementing these measures. Even more importantly, states should use this experience to create a more equitable and effective healthcare system that supports all populations.

CLIMATECHANGE:

HEALTHCARE?SNEXT BIGGESTTHREAT

W RITTEN BY DHIVYA ARASAPPAN DESIGNED BY FARHAANAH MOHIDEEN

From wildfires to cold snaps, we?ve come to see the undeniably real consequences of climate change on our lives in this past year. In Califor nia, a record 4 million acres of land bur ned through by October, 2020 which is more than double its previous record1 and in Texas, not three months ago, freezing temper atures for the fir st time in decades caused many to face water shor tages and power outages. Extreme weather events are cer tainly one of the more visible aspects of climate change, and while these events are projected to occur more frequently and intensely,2 Amer icans tend to view climate change as less threatening to their health than to the health of other s.3 But just how does climate change impact health? One par ticularly salient example is of the Califor nia wildfires from early 2020. According to the CDC, wildfire smoke is composed of a number of har mful par ticulates from carbon monoxide and nitrogen oxides to other volatile or ganic compounds.4 Prolonged exposure has been shown to increase respir ator y and cardiovascular hospitalizations, and higher r ates of asthma, bronchitis, chest pain and respir ator y infections.5 Increasing levels of pollution results 16 in greater r isk of life threatening attacks for those 16

with asthma while also elevating the r isk of hear t disease and stroke. Many of these health consequences of climate change were recognized and explored close to 20 year s ago in a 2002 paper titled ?Global Climate Change and Health: Challenges for Future Pr actitioner s? which remain incredibly relevant to today?s challenges. One "Cl imat e impor tant point r aised was in regard to the changeis not impact of increasing l onger j ust a ambient temper atures with vector bor ne t hr eat f or pathogens. In essence, as our a result of the war ming climate, we are likely to f ut ur e? it see an increased has enor mous incidence of infectious diseases? par ticularly impl icat ions those tr ansmitted by f or our v er y mosquitoes? such as Zika, pr esent " West Nile, dengue and malar ia, which are more likely to begin to appear in temper ate zones.6 Increasingly, researcher s and 18

policymaker s alike are beginning to realize that the health consequences of climate change are not just limited to respir ator y or infectious disease. Mental health is just as affected. A recent study on over 18,000 Amer icans with cognitive impair ment published in JAMA Neurology repor ted a strong association between exposure to high levels of air pollution and the r isk of developing dementia.7 Climate change is no longer just a threat for our future? it has enor mous implications for our ver y present as existing health threats are expected to intensify and new ones emer ge. In recover ing from the COVID- 19 pandemic and rethinking how our healthcare systems can increase their resilience and reach, we must not only respond to the challenges of the pandemic but also equip our healthcare system to handle the stresses and threats posed by climate change on human health. Extreme weather events such as

these and gener al effects of climate change from increasing temper atures to air pollution levels have a direct impact on the health of our communities. But the gener al widespread of climate change such as small changes in the aver age temper atures can result in big changes in the frequency of extreme temper atures. And on top of that, the har mful impacts on health are ?most likely to occur where extreme weather and population vulner ability conver ge.?8 At the end of the day, the question at the top of our minds is simply, what can we do? Introduce institutions that will have climate change effects of health at the forefront of their policy and research effor ts. One step is to create a National Institute of Climate Change and Health. Author s Howard Fr umkin and Richard Jackson ar gue that by increasing research and funding for climate change and health with a singular focus on the climate dr iven effects on health, we can begin to gain the knowledge to create better, more effective and comprehensive policy.

Lear ning from our response to the COVID- 19 pandemic, it is par ticularly cr ucial to under stand that "at t heend of climate change has a t heday, t he differential impact on the most vulner able, quest ion at which often includes t het op of our communities of color. minds is Refor ming our healthcare system simply, what with an eye on can wedo?" vulner able communities and how they are affected by poor housing, access to healthcare, and discr imination in the healthcare system are all socially relevant components that will impact the health of these communities in year s to come. Young children, pregnant women, older adults, people with chronic illnesses and disabilities, outdoor worker s, as well as minor ity populations and low socioeconomic status are impor tant indicator s of which groups of people will be severely impacted by climate change.9 We've already seen examples of this from Texas and Califor nia in the past year. If this goes on without being addressed, it will leave lasting impacts on the Amer ican healthcare system in the future. 18 18

THE C VID- 19 NURSING SHOR

Wr itten By: Eesha Balar | W ith the thought of COVID-19, most people are quick to think about the increasing death rates, the vaccine, or even patients they personally know affected by the virus. However, what is often overlooked is the behind-the-scenes impact of the pandemic? the toll on staffing and how the workforce and allocation of responsibilities have shifted. There are many staff involved in maintaining a functioning, organized, and efficient hospital environment? even beyond the physicians and specialists the public commonly knows. There are registered nurses, nurse practitioners, pathologists, surgeons, anesthesiologists, lab technicians, various types of therapists, and other personnel dedicated to ensuring patients are properly cared for.1 In a typical year without the pandemic, their work conditions would have been predetermined based on their specialty. However, the responsibilities of the majority of these workers have increased tremendously due to COVID-19. For example, anesthesiologists and other hospitalists with relatively unrelated responsibilities have had to stretch their skillset to take care of patients in critical condition, such as those on ventilators.2 Arguably, the worst consequence of the pandemic thus far on the structure of healthcare teams is the overall staffing shortage, especially for nurses. The magnitude of the shortage can be described from an economics perspective. Research conducted by Joshua Gottlieb, a professor at the University of Chicago, indicates that in the early stages of the pandemic, beginning in March 2020, there was a large spike in demand for nurses. It was specifically found that the number of ICU, or intensive care unit, jobs for nurses increased by a staggering 339%, with the corresponding wage increasing by 50%. In similar

ISSUE # 2232 20

divisions of the hospital in which the pandemic brought on a greater volume of patients, such as the emergency room, the number of job openings increased 89%, with the salary increasing by 27%.3

However, even with the prospect of a higher wage for nurses, the risks are simply not worth the extra hospital hours, high-stress environments, and questionable protectable protection from the virus itself.4 According to a report from March 2020 by the U.S. Department of Health and Human Services, the psychological effect of working in the hospital at this time is quite significant. W orkers experience heightened anxiety in a personal and professional sense due to the fear of contracting the virus and spreading it to loved ones, as well as because of the decisions that need to be made in treating patients with a novel virus.5 W hile the greater need of nurses is primarily due to increased patient volume in hospitals, it can be argued that these concerns Source: Gottlieb, Joshua may be driving many employees and nurses to step down from their jobs. Additionally, the job market for nurses is quite elastic with regards to wage. W ith fluctuating wage value as a considerable factor, compounding the persistent demand for nurses in the market, there has been an increase in the number of traveling nurses, who serve more flexible hours in hotspot areas of the outbreak and are generally provided with slightly higher wages than in the hospital, better protection from the virus, and housing privileges.6,

RTAGE AND ITS IMPLICATIONS

| Designed By: Alyssia Liu 7 At

the same time, however, these nurses are faced with an uncertain trajectory and fluctuating wages? their future work depends on the agency they sign with, which comes with fixed, hard-to-negotiate salaries. W hile it may seem that the reallocation of workers would be beneficial for the pandemic, there is a need overall for nurses, in rural and urban areas, as well as in those not particularly affected by COVID-19. One major effect of this increase in traveling nurses is the crisis seen in rural hospitals.

According to a study done by the University of North Carolina, 2020 alone brought about the closure of 20 rural hospitals in the United States, a record for the annual number of closings, primarily due to the virus.8 As further commented upon by a panel of rural health experts at Penn?s Leonard Davis Institute of Health Economics, moderated by Dr. Joanna Hart, the head of the institute?s Rural Health and Policy Research W orking Group, most rural hospitals are unable to a D. and Zenilman, Avi, 2020 continue paying for expensive and necessary medical equipment, such as ventilators and wages for nurses and other healthcare providers, causing many employees to leave. Consequently, the presence of only a few COVID cases in these hospitals has become overwhelming.9 As a result, attracting the attention of such healthcare workers is crucial for these clinics to continue running.

mentioned previously, the pay offered by many hospital systems is increasing as a way to attract workers? attention. W ith registered nurses making up the majority of healthcare labor, temporary nurses are being actively sought out by healthcare systems with more privileges as an incentive. Furthermore, there is controversy surrounding nursing programs for college students, with many people disapproving of their consistently high selectivity in admissions, exacerbating the current demand for nurses and raising the concern of whether students will continue enrolling in such programs or not. The primary factors driving this phenomenon are the lower wages of faculty members brought on by the pandemic, as well as the inability of hospitals to allow students to do their rotations safely in the workplace. However, it is still debated whether more students should still be admitted and partially trained as a solution to the persistent demands in the overall market.10 Although the maintained selective admissions by college programs may cause the nursing labor force to remain stagnant, many universities are being turned to as resources of medical or nursing students. In many colleges, such as the University of W ashington, students with a medical background are offered $500 tuition credit for working at hospitals dealing with staffing shortages and for delivering COVID vaccines. Training has likewise been made easier for such students with online sessions making this a temporary, yet valid, solution to labor issues.11 W ith many healthcare and community service organizations looking for college students to volunteer, perhaps we, as Penn students, can take this opportunity to fight back against the spread of the virus by helping with the underlying shortage in the healthcare workforce.

W hen considering the effects of the nursing shortage, what changes are being made to alleviate its consequences? As

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TheFutureof Alzheimer?s Disease Treatment Written By Leeyu Addisu Designed By Alyssia Liu

Alzheimer?s, also known as ?the most feared disease in America?, is the sixth leading cause of death, and the leading cause of dementia in the USA. Between 2000 and 2014, Alzheimer?s disease (AD) deaths in the US have increased by 89%,1 partially due to the aging baby boomer population. Progression of the disease is divided into 7 stages, ranging from no impairment to very severe decline. Many patients experience distraction, memory loss, agitation, depression, hallucination, and finally, the complete loss of function and death. The progression from early diagnosis to death can take anywhere from 3 to 9 years. Currently, Alzheimer?s disease can only be diagnosed definitively post-mortem, with 22

the presence of amyloid beta plaques and neurofibrillary tangles. Upon the onset of initial symptoms and failure of

"Congress has granted $1.4 billion for Alzheimer's research in the hopes of having a disease modifying therapy by 2025." a mini mental exam, patients are generally referred to a neurologist to rule out secondary causes of memory loss, such as vitamin B deficiency or syphilis. They also undergo imaging of the

brain to establish a baseline for degradation. On average, patients with AD experience 3-5% loss in hippocampal volume per year, as opposed to 1% in non-AD patients of the same age. AD diagnosis is an area of intense research, and many in the field believe that early diagnosis and slowing the aggregation of tau (a microtubule associated protein) caused by hyperphosphorylation will be the key to finding a cure. In addition, it?s not well understood exactly what causes the onset of Alzheimer?s disease.2 There are over a dozen hypotheses, including mitochondrial cascade, oxidative stress, and even metal imbalance. Cholinesterase inhibitors and NMDA receptor antagonists, the current standard of

Alzheimer?s care, are not informal care at home. Each blood by promoting its disease-modifying. In other year families provide an secretion via urine. Recently, a words, they do not stop estimated $18.5 billion worth successful preclinical study neuronal of unpaid care testing the effect of an degeneration. services to those Alzheimer?s vaccine on mice Congress has with AD. 25% of has created hope for the granted $1.4 billion caregivers also millions suffering with "There are 5 for Alzheimer's for a child Alzheimer?s. This vaccine, currently 333 care research in the under 18, designed to trigger antibodies hopes of having a active clinical increasing their against beta-amyloid in the disease modifying risk of brain, was found to be trials for therapy by 2025. depression and effective in the mouse model, Alzheimer's This is estimated to anxiety. improving memory test save payers $367 Treatment with performance. If effective in disease in billion by 2050. The memantine and humans, the Alzheimer?s the United cumulative costs to cholinesterase vaccine could drastically all payers for the inhibitors improve the lives of those States." care of Americans (donepezil, suffering from the disease, living with rivastigmine, and even possibly prevent Alzheimer?s over galantamine) development of the disease in the 2015-2050 period will be increases direct medical healthy adults. $20.8 trillion, nearly 70% of costs, but is cost saving in the Beyond the scientific front, a which will be borne by federal long term as it increases political battle is being fought and state governments.3 patient independence and by AD activists. Organizations Caring for a family member shortens the duration of final like the Alzheimer?s with AD can be very institutionalization compared Association are campaigning expensive, and becomes to no treatment. for Medicare more expensive as the There are currently reform to disease progresses and 333 active clinical benefit those "Each year patients require more care. In trials for who are the early stages, an AD Alzheimer?s currently and families patient is usually able to disease in the will potentially provide an complete many tasks United States. be impacted by themselves with supervision Many of the drugs Alzheimer?s estimated and is cared for by family or in clinical trials are disease.6 $18.5 billion home care workers. As the repurposing Recent laws like 4 disease progresses, the candidates. One the BOLD worth of patient may transition to living such drug is Infrastructure unpaid care in a residential care facility nilotinib, a tyrosine for Alzheimer's that offers 24/ 7 supervision kinase inhibitor Act work to services to and help with medical needs. used for chronic help provide those with AD." Once the patient has reached myeloid leukemia access to early the final stage of their disease (CML). It triggers detection and and loses awareness, they will autophagy, and data collection transition to hospice care researchers hope that it can to analyze behavioral risk where trained nurses and be used to clear out beta factors. Political reforms like palliative care physicians will amyloid plaques. Another these as well as scientific provide for their medical potential treatment is developments will make a needs when they are no Dapagliflozin, a drug used to great impact in the lives of longer able to communicate. treat type 2 diabetes, which those battling AD now and in 22 80% of AD patients receive decreases glucose in the the future. 22

Heal t hcar eTr ends Ov er t heNext Decade W r itten By Rajat Ram esh Design ed By Sh aan Patel

ver the last several years, changes in the healthcare industry have been indicative of the industry's evolution in years to come. Transformational factors, including value-based care and the increased use of telemedicine and analytics are crucial for the refinement of the U.S. healthcare system. Furthermore, changes in infectious disease control and the management of the transition from fee-for-service to alternative payment and delivery models must be considered when analyzing the healthcare industry in the next decade.

VALUE- BASED CARE The transition to a value-based healthcare system is a slowly unfolding fundamental change that is marked by an increase in available data. Dan Mendelson, founder and former CEO Avalere Health, believes that healthcare providers will be important for this transition: ?In an increasingly capitated environment, providers will bear more responsibility for these outcomes and for engaging positively with consumers.?1 This is due to an increase in the percentage of Americans enrolled in Medicare Advantage, a health insurance plan that provides benefits through a private-sector health insurer. Thirty years ago, in 1991, about 6% of Americans on Medicare utilized Medicare Advantage. Today, around 36% of those on Medicare benefit from Medicare Advantage, and the growth rate is steadily increasing at a rate of around 8% a year.2 These numbers indicate that Medicaid is expanding into managed care (a type of health insurance that has contracts with health care providers and medical facilities to provide care for members at

reduced costs),3 and that the U.S. government is strongly interested in value-based healthcare.

and the ability to personalize medicine based on associated demographics could lead to an improvement in the overall quality of healthcare.

DATA & ANALYTICS Due to the COVID-19 pandemic, it is expected that telemedicine and analytics usage in healthcare will increase more than ten-fold.4 While the Internet may have insufficient safeguards for confidentiality, telemedicine and electronic medical records provide an efficient practice to store information. Some doctors such as Richard Boxer, MD, FACS, believe that telemedicine will fill an important gap in healthcare: ?Telemedicine can be a lifesaver for the 100 million people in rural America who are not near a healthcare facility. It?s been shown repeatedly that at least 25% of all healthcare can be delivered via the telephone or video conferencing?.5 Like value-based care, telemedicine

INFECTIOUS DISEASE CONTROL AND MANAGEMENT COVID has shed light on the necessary reform in infectious disease control and integrated management protocols. With the politicization of pandemic response in the United States6 accompanied by the undermining of public health measures, it is clear that public confidence in science-based health policy has decreased. This must change. Part of the distrust stems from the large disparity in healthcare access and income, with many underserved demographics

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disproportionately impacted by coronavirus.7 The One Health initiative, a coordinated and cooperative effort across the animal, human, and environmental sectors, is essential in tackling the rising threat of infectious disease. With an expanded social safety net of health insurance, a first step can be taken to deal with the current inequities. Furthermore, a sound foundation to underpin health insurance should reinforce science-driven governmental actions. For example, the increased use of data across health platforms to track the role of environmental indicators in zoonotic disease can inform decision-making and streamline federal, local, and state action.8 In this 26

decade, U.S. engagement and leadership in global settings to address future pandemic threats must be initiated to prevent a public health crisis of this magnitude from occurring again.9

ALTERNATIVE PAYMENT AND DELIVERY MODELS Fee for service payment models are notorious for creating perverse incentives that prioritize profit over patient health. The good news is that there is a trend of transitioning away from fee-for-service to alternative payment and delivery models which is expected to correlate with the improved availability of data to the public and better health outcomes. Particular medical practices, including surgical operations, will likely

improve or be removed from institutions based on its efficacy and value to the patient. With an emphasis on data-driven approaches, patient care should become more regularized, allowing for the development of the best delivery model.10 For example, Arthur Garson, Jr, MD, MPH, states that ?it will be possible to measure the outcomes of nurse practitioners, generalist physicians, and specialty physicians in the management of certain diseases and determine the best utilization of each?.11 In terms of payment model, increased quantities of patients should lead to a larger demand of practitioners, and payment will be predicated on the optimization of care for a larger pool of patients rather than who is taking care of certain patients.

Scan th e QR code to access al l r efer en ces an d im age citation s:

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WHARTON UNDERGRADUATE HEALTHCARE CLUB

Penn Heal t hcar eRev iew

This is a student-led initiative; all articles were written and edited by Penn undergraduates and therefore do not reflect the opinions of WUHC or the University of Pennsylvania.