Neffy: A Needle-Free Future For Allergy Emergency Care

For those with food allergies, every meal is a potential life-or-death situation. Yet throughout history, allergies were poorly understood and rarely treated. Reports from ancient China, Rome, Egypt, and Greece confirm that antibody-antigen interactions have existed for millenia, though the term “allergy” was only coined in 1906, by Clemens von Pirquet [1]. Despite their prevalence, scientists only came to understand the mechanisms behind allergies in the middle of the 20th century; in 1967, the crucial antibody immunoglobulin was identified. The modern standard of care, the EpiPen epinephrine auto-injector, was patented in 1977 and FDA approved in 1987 [1, 2]. Since then, the Epipen has revolutionized the treatment of severe anaphylactic shock and has saved countless lives. Nonetheless, epinephrine delivered via injection comes with challenges regarding needle use, administration complexity, and accessibility. 

Neffy, a new nasal epinephrine delivery system, represents a promising advancement in allergy medicine administration by offering a needle-free option that could significantly impact emergency care for anaphylactic patients. By improving the public’s ability to administer epinephrine quickly and effectively, Neffy could positively affect anaphylaxis response times and survival rates. However, these benefits must be weighed against considerations of safety and equitable access.

With the current standard of care being injectable forms of epinephrine, people with allergies may be intimidated about using their delivery systems. In particular, many children face challenges with epinephrine auto-injectors due to needle phobias. Neffy provides a less threatening alternative: a nasal spray which might improve the willingness of patients and caregivers to administer life-saving treatment promptly. According to a survey of patients and caregivers, “72% would prefer using an epinephrine nasal spray instead of an auto-injector” [3]. Willingness to administer epinephrine has substantial effects on survival rates, as “delayed use of epinephrine during an anaphylactic reaction has been associated with deaths” [4]. Additionally, the nasal spray is both user-friendly and FDA approved, showing “greater or similar” efficacy to an auto-injector [3]. Finally, the cost provides an added benefit for those without insurance coverage—a package of 2 auto-injectors costs approximately $600-750, whereas 2 of the Neffy nasal sprays cost $498 [3,5]. Overall, a nasal delivery system may be a very attractive option to many people with severe allergies.

Despite these benefits, Neffy’s use raises ethical concerns, particularly regarding safety and efficacy. Since Neffy is a newer technology, it is crucial to evaluate whether it delivers epinephrine as effectively as injectables; the FDA approved it based on four studies (on healthy adults without anaphylaxis), but new evidence may come out to the contrary. Additional clinical trials should be done verifying Neffy’s effectiveness in patients actually experiencing anaphylactic shock, rather than just measuring epinephrine absorption. One of the biggest questions raised is whether one should prefer Neffy to a traditional auto-injector in an emergency. Many patients have used EpiPens for years and are comfortable with using them. For those who still carry an EpiPen but have decided to purchase Neffy, the dilemma of deciding between a trusted medication and Neffy may cause hesitation in a moment of distress. Even if patients carry both, they and their caregivers should have a clear plan in mind of which delivery system they plan to default to. One final concern lies with access equity: though the cost of Neffy and other innovative nasal therapies appear to be manageable, asymmetric distribution in the next few years might leave certain areas without access. Nevertheless, this is the case with many innovative treatments; with time, Neffy and other alternative nasal epinephrine delivery systems will hopefully become widely available. 

With its nasal spray design, Neffy could increase accessibility and lower rates of medical errors by reducing the complexity of epinephrine administration. However, ensuring its efficacy remains crucial, as does conducting rigorous clinical trials to confirm its reliability. Future research and policy initiatives will play key roles in Neffy’s adoption. Should these concerns be addressed, Neffy has the potential to become a staple in life-saving allergy care, giving peace of mind to millions who worry about allergies daily.

Reviewed by Abby Winslow

Graphic by Haynes Lewis

References

1. https://www.nationalgeographic.com/science/article/partner-content-brief-history-of-allergies 

2. https://pmc.ncbi.nlm.nih.gov/articles/PMC10052460/#:~:text=Epinephrine%20has%20been%20certified%20for,as%201901%20for%20medical%20use.&text=The%20recommended%20dosage%20varied%20broadly,to%20treat%20anaphylaxis%20in%201987.

3. https://allergyasthmanetwork.org/news/epinephrine-nasal-spray-for-anaphylaxis/ 

4. https://dph.illinois.gov/topics-services/prevention-wellness/epinephrine-autoinjector-and-anaphylaxis.html#:~:text=Epinephrine%20is%20a%20highly%20effective,has%20been%20associated%20with%20deaths.

5. https://www.goodrx.com/epinephrine-epipen/how-to-save-cost?label_override=undefined

The Cost of Thinness: Socio-Cultural Forces Behind Anorexia Nervosa

In societies that champion health and well-being, what drives so many young lives towards a relentless pursuit of thinness, even to the brink of death? Anorexia nervosa (AN) is a severe psychiatric disorder associated with “aberrant patterns of feeding behavior and weight regulation, and deviant attitudes and perceptions toward body weight and shape”.1 In industrialized countries, eating disorders are the third most common chronic disease in female adolescents. In Western countries, the rate of AN is 0.3%.2 AN sees a high prevalence among adolescent females, yet it is multifaceted in its causation, with complex intersections of biology, psychology, and socio-cultural dynamics. Notably, this disorder has the highest mortality rate of any psychiatric condition: approximately 5% of individuals diagnosed with anorexia die within the first four years of diagnosis. Morever, AN is associated with various causes of death: suicide, pulmonary disease, diabetes, liver and other digestive disease, to shock and organ failure.3 While studies indicate that genetic factors account for approximately 40-50% of the risk for developing AN,  social components still play a key role by exposing individuals to distinct environments that can lead them to developing this devastating eating disorder.4 

Although twin studies show that genetics contribute by establishing personal traits that may increase vulnerability to AN, the primary factor remains the social environment individuals are immersed in. Historically, socio-cultural factors—especially those tied to body image and ideals of thinness—have strongly influenced the development and persistence of anorexia nervosa, forming a complex situation that demands more than clinical treatment alone. Discussions on the socio-cultural origins of AN date back to 19785, but in the 50 years since few actionable solutions have been implemented to curb its prevalence.  A cultural shift in societal standards of beauty and success is vital to disrupt the cycle that continues to trap at-risk individuals.

The societal conditioning towards thinness is alarmingly powerful. Although there is a "window of opportunity" for successful treatment during the first few years of the disorder, most young people seek help well after the eating disorder has taken root for early intervention to be effective, in part due to socio-cultural forces..6 The Tripartite Model of body dissatisfaction indicates that the sociocultural emphasis on thinness is reinforced by media, parents, and peers.4 Mass media campaigns propagate an “ideal of beauty” that endorses thinness for women, equating slenderness with success and appeal and influencing individuals, often beginning at a young age, to internalize these ideals. As Uchôa et al. reveal, a significant 45.3% of adolescents report being moderately influenced by the media. Unsurprisingly, girls are more affected, with 25.7% experiencing pronounced media influence compared to 19.6% of boys.2 These media-driven ideals exacerbate body dissatisfaction and pose an increased risk for eating disorders during a vulnerable developmental period.

The cultural contagion of disordered eating behaviors is also seen through peer dynamics. During adolescence, female friendship circles can cultivate an unhealthy focus on dieting and weight loss. Peer discussion and the ensuing social validation for losing weight often leads to a group-sanctioned pursuit of thinness, which solidifies the unhealthy idea that thinness equals beauty, within individuals. In such environments, anorexia nervosa can soon develop as adolescents strive to belong or stand out within these social hierarchies. The disorder, for some, can even become a source of identity, offering a sense of distinction and accomplishment where many peers might falter in their dieting efforts. By succeeding where others fail (at dieting, self-discipline and thinness), “the progression towards an eating disorder offers the appeal of a new adolescent identity and social distinction in the group”.6 The sense of success is further strengthened if one has genetic predisposition of having the following traits: perfectionism, the desire to correspond to a certain ideal image of oneself, instability of Ego, unstable identity violations, and reduced ability to form a picture of the future and themselves in the future.7 Personal vulnerabilities, amplified by genetic predispositions, can heighten susceptibility to the environmental triggers discissed.4

Further, these environmental triggers of anorexia nervosa are not confined to Western societies or Caucasian populations. In fact, binge eating and purging behavior are reported among Black women at least as frequently as among White women, yet AN is rarely found among Black women.8 However, differences in the prevalence or rates of occurrence of eating disorders among individuals or social groups do not mean that they are not at risk.9 Willemsen and Hoek present a case of a Black woman from Curaçao who developed AN after moving to the Netherlands. Initially, she conformed to Caribbean ideals that celebrated fuller figures, but upon exposure to Western beauty norms that idolize thinness, she changed her perception of self-worth. Mainly through television, she noticed that in the Netherlands being thin is considered attractive and that many Dutch women diet. As a result, she decided to pursue dieting and later was admitted with the AN diagnosis. This case illustrates that the patient’s ethnic background did not protect her from developing AN. It highlights the contribution of sociocultural influences, in the form of local norms regarding body size and shape, towards the development of AN. There is danger in taking too seriously the idea that some groups, particularly African-American women, are “protected” from eating problems. Assigning “immunity” to a specific group could result in the misdiagnosis and under-representation among people of different gender, racial, ethnic, sexuality and class backgrounds with eating disorders.9

Although some individuals with anorexia find a sense of community within their disorder, the stigma and isolation surrounding anorexia present substantial barriers to recovery.6 The friendships that persist at earlier stages of the disorder are frequently lost rapidly as the condition progresses, leaving the person socially isolated. Once anorexia becomes entrenched, patients often find themselves alienated from peers and friends. “Unlike other illness categories, anorexia nervosa was transformed from a clinical entity into a friend: it became Ana, a comforter – especially during the early ‘honeymoon phase’ of the disorder,” Allison et. al say.  For some, anorexia nervosa forms a sense of distorted community, where “shared experiences in inpatient or day patient settings create a 'team activity' atmosphere with its covert rules”.6 The false of community that AN patients might find themselves engulfed in, delays seeking treatment or even makes treatment impossible, as the condition often becomes self-reinforcing, embedded within a sense of belonging and understanding that the disorder falsely provides.

In addition to media and peer influences, economic and political factors are also associated with control over women's bodies. The perpetuation of the thin ideal is as much an economic construct as a cultural one, perpetuated by industries that profit from women's insecurities about their bodies. These industries promise empowerment through self-improvement and control over one’s eating habits and weight — ideals that resonate with but limit women's autonomy by keeping them focused on unattainable body standards, diverting time, money, and energy away from pursuits that could foster true empowerment. This self-imposed societal pressure creates a cycle of control that aligns with patriarchal capitalism, leaving few avenues for women to escape unless systemic changes are made in how beauty and success are marketed.9

However, socio-cultural factors cannot be viewed independent of  the individual psychological and genetic predispositions that heighten the risk of AN development. Research indicates that genetic influences account for over 40% of the variance in thin-ideal internalization.4 This genetic inclination combined with persistent socio-cultural messaging creates a fertile breeding ground for anorexia to thrive. While society may normalize thinness as beauty, not everyone will internalize this standard to the same pathological extent, illustrating an interesting battle between nature and nurture in the development of eating disorders. The differences in how individuals internalize beauty standards highlight the influence of diverse socio-cultural environments. In recent years, researchers have explored programs aimed at attempts to mitigate the development of AN.

A 2022 study conducted in the Netherlands found that positive body exposure, administered with the Positive Body Experience protocol, leads to “significant positive changes in attitudinal body image, eating pathology and depressive symptoms in female participants with eating disorders”, including anorexia nervosa “in a clinical setting”.10 However, what happens when the patients go back to their pre-clinical lives? Will the eating disorder return given the exposure to the same environments, social pressures, and media? Ultimately, resolving the pervasive issue of anorexia nervosa requires a holistic approach, addressing not only the individual psychological predispositions and AN patient’s environments but also the societal structures that engender these disorders. 

The cost of thinness—embodied in the experiences of those struggling with anorexia nervosa—reveals a mixture of socio-cultural forces and individual genetic vulnerabilities. Acknowledging the complexity of these influences is an important step towards creating a more empathetic, informed, and equitable society where individuals are valued for their intrinsic worth rather than their adherence to unrealistic and harmful body ideals. The road to recovery and prevention is not short, nor is it without its challenges. Fundamental societal change necessitates systemic solutions that go beyond individual therapy but rather incorporate economic, political, and educational reform, reshaping the way beauty is perceived in our cultures. The ethical implications are clear. Healthcare providers must address both the biological and sociocultural dimensions of AN, while society at large must recognize its role in contributing to environmental conditions that can activate genetic vulnerabilities. Only by confronting the deeply ingrained socio-cultural forces and challenging the lucrative industries that benefit from persistent body dissatisfaction can we hope to alleviate the suffering of those grappling with AN and prevent future generations from falling into these unhealthy norms.

Reviewed by Anna Chen

Graphic by Eugene Cho

References

1. Kaye W. Neurobiology of anorexia and bulimia nervosa. Physiol Behav. 2008;94(1):121-135. doi:10.1016/j.physbeh.2007.11.037

2. Uchôa FNM, Uchôa NM, Daniele TM da C, et al. Influence of the Mass Media and Body Dissatisfaction on the Risk in Adolescents of Developing Eating Disorders. Int J Environ Res Public Health. 2019;16(9):1508. doi:10.3390/ijerph16091508

3. Auger N, Potter BJ, Ukah UV, et al. Anorexia nervosa and the long‐term risk of mortality in women. World Psychiatry. 2021;20(3):448. doi:10.1002/wps.20904

4. Suisman JL, O’Connor SM, Sperry S, et al. Genetic and environmental influences on thin-ideal internalization. Int J Eat Disord. 2012;45(8):942-948. doi:10.1002/eat.22056

5. Garner DavidM, Garfinkel PaulE. SOCIOCULTURAL FACTORS IN ANOREXIA NERVOSA. The Lancet. 1978;312(8091):674. doi:10.1016/S0140-6736(78)92776-9

6. Allison S, Warin M, Bastiampillai T. Anorexia nervosa and social contagion: Clinical implications. Aust N Z J Psychiatry. 2014;48(2):116-120. doi:10.1177/0004867413502092

7. Balakireva E, Zvereva N, Voronova S. Personal and clinical traits in adolescents, diagnosed with «anorexia nervosa». Eur Psychiatry. 2021;64(Suppl 1):S356. doi:10.1192/j.eurpsy.2021.953

8. Willemsen EMC, Hoek HW. Sociocultural factors in the development of anorexia nervosa in a black woman. Int J Eat Disord. 2006;39(4):353-355. doi:10.1002/eat.20234

9. Hesse-Biber S, Leavy P, Quinn CE, Zoino J. The mass marketing of disordered eating and Eating Disorders: The social psychology of women, thinness and culture. Womens Stud Int Forum. 2006;29(2):208-224. doi:10.1016/j.wsif.2006.03.007

10. Rekkers ME, Aardenburg L, Scheffers M, Elburg AA van, Busschbach JT van. Shifting the Focus: A Pilot Study on the Effects of Positive Body Exposure on Body Satisfaction, Body Attitude, Eating Pathology and Depressive Symptoms in Female Patients with Eating Disorders. Int J Environ Res Public Health. 2022;19(18):11794. doi:10.3390/ijerph191811794

A Pill for Time: The Promises and Perils of Rapamycin

1:12. 0:43. 0:21. Each morning, countless Americans open their New York Times app, fingers hovering over the Mini Crossword, ready to shave off mere fractions of a second from their personal best time — a daily ritual of racing against the clock, pursuing an elusive new record. Down to 0:19. Then 0:18. The thrill of watching the clock tick lower and lower.

Our obsession with time isn’t limited to daily puzzles; it extends to the ultimate race: the quest for a longer life. This pursuit is anything but new — humans have been trying to outmaneuver death since we first became aware of our own mortality. From ancient Egyptian hieroglyphs to Chinese alchemical texts, from Plato's musings to Aristotle's contemplations, the dream of extending life has echoed through millennia of human civilization. However, what took centuries of philosophical pondering to even conceptualize has now quickly become a reality through scientific advancement. In short, modern medicine has transformed the abstract theories of Plato and Aristotle into concrete gains. At the beginning of the 19th century, no country's life expectancy exceeded 40 years, but today, the global average life expectancy is estimated to be 72.6 years [3]. Although life expectancy has increased across all ages, most of our dramatic gains in average lifespan have come from technological and medical breakthroughs focused on preventing early deaths — keeping infants alive, curing infectious diseases, and making childbirth safer.

Consequently, modern medicine has been so successful in curbing death rates among the young that we've nearly exhausted all possible improvements in early-life mortality. Now, researchers must shift their focus to a new frontier: preventing deaths in old age itself. Unlike preventing early mortality, extending life in old age means confronting bodies that have accumulated decades of biological wear and tear, where cellular damage, chronic inflammation, and deteriorating systems create a maelstrom of mortality risk. In other words, each additional year of life expectancy has become increasingly harder to achieve.

This challenge has led scientists down an unexpected path as researchers have begun to focus on tackling old age from its roots: can we slow aging itself? The answer may lie in an unlikely source. Rapamycin, first discovered in the soil of Easter Island, isn't a mythical fountain of youth —but its effects may have the potential to change how we experience aging itself.

Historically, Rapamycin has been used as an oral immunosuppressant for organ transplant patients. Recent research has uncovered, however, that at low doses, rapamycin appears to reduce inflammation by inhibiting the mTOR signaling pathway, which serves as a critical regulator of aging and the body's lifespan [1]. Inspired by this discovery, scientists such as Dr. Matt Kaeberlein have started testing in animal models, with results indicating that rapamycin usage in mice can result in up to a 30% increase in lifespan [2]. Further research has proved even more successful, as shown in a trial where a one-time 3-month dosage of rapamycin in mice resulted in longer life and substantial improvements in murine heart function [2]. Due to the extensive genetic similarities between mice and humans, scientists have started to hypothesize that rapamycin may have similarly beneficial effects on human life spans.

Despite promising results in animal models, significant hurdles remain before rapamycin can be considered a viable option for improving human longevity. The long-term effects in humans are still unknown, and an optimal dosage for anti-aging purposes has yet to be established. Complicating matters further, the FDA doesn't currently recognize aging as a disease, which means that 1) drugs targeting aging specifically aren’t eligible for approval as treatments, and 2) clinical trials using rapamycin are plagued by ill-fitted regulatory constraints. Thus, leading researchers on aging and rapamycin, including Dr. Matt Kaeberlein and Dr. Eric Verdin, publicly advise against using rapamycin for life extension. The twist? They are taking it themselves, prescribed off-label [4]. 

The actions of leading longevity researchers speak louder than their words. Dr. Kaeberlein and Dr. Verdin's actions serve antithetical to their public advice. But why? For them and many others, they don't have enough years left in their lives to wait for conclusive results from long-term studies; it's now or never. So, while unapproved, is it safe to bet on rapamycin extending your life without knowing its long-term impacts?

The answer varies for each individual, but regardless of personal choice, rapamycin represents a concerning shift in our approach to longevity — the pursuit of potentially harmful quick fixes over proven routines. While exercise, nutrition, and lifestyle modifications require consistent effort, they build a foundation for comprehensive health that extends beyond mere lifespan. Rapamycin, in contrast, offers a seductive shortcut that bypasses these holistic benefits. By reducing the complex journey of healthy aging to a pill, we not only risk oversimplifying the multifaceted factors that contribute to longevity but also ignore the importance of lifestyle, environment, and social determinants of health in favor of quick pharmacological fixes.

However, the strongest argument against rapamycin’s usage lies in its potential to deepen America's already severe health disparities. Off-label prescriptions and high costs mean that even if rapamycin proves effective for human longevity, its benefits will flow primarily to the wealthy. This accessibility issue creates an unprecedented form of inequality where money doesn’t just buy better healthcare, but also more years of life itself. In an increasingly costly healthcare environment, the wealthy already enjoy longer lives due to better access to healthcare, nutrition, and healthy lifestyles. Adding rapamycin to this equation would only widen the existing life expectancy gap, fostering a society where longevity becomes a luxury good rather than a human right.

Crucially, the most urgent step isn't deciding whether to take rapamycin; rather, it is reconsidering how we view aging itself. Our current regulatory framework, which doesn't recognize aging as a disease, creates a pharmaceutical catch-22: we can't properly study anti-aging treatments because aging isn't classified as a treatable condition, yet we hesitate to classify it as such because we lack proven treatments. Breaking this cycle requires a fundamental shift in how we conceptualize and regulate aging intervention research. Only by acknowledging aging as a medical condition—rather than as an inevitable decline—can we create the regulatory framework needed to properly study, develop, and equitably distribute treatments like rapamycin.

Until then, we're left with an uncomfortable reality: a promising compound that sits in regulatory limbo, prescribed off-label by those who can afford it, while the broader implications of its use remain underexplored. Ultimately, the debate around rapamycin isn't just about a potential life-extending drug—it's a mirror reflecting our society's complex relationship with aging, inequality, and the lengths we'll go to add a few more numbers to our personal timers.

Graphic by Monica Rashkov

Reviewed by Nick Hoffmann

References

1. Abuery, A. (2024, July 1). Could a decades-old transplant drug unlock the secret to longer life? NPR. https://www.npr.org/sections/shots-health-news/2024/07/01/nx-s1-5008777/rapamycin-aging-disease-drug-humans-research

2. Kaeberlein, M. (2024, January 15). Rapamycin: The most promising life extension drug [Video]. YouTube. https://www.youtube.com/watch?v=DcxgEwQKx8Q

3. Roser, M., Ortiz-Ospina, E., & Ritchie, H. (2024). Life Expectancy. Our World in Data. https://ourworldindata.org/life-expectancy-globally

4. Whalen, J. (2024, March 15). A transplant drug shows promise for extending life. Should you take it? The Washington Post. https://www.washingtonpost.com/business/2024/03/15/rapamycin-longevity-drug/