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Insulin is a life-saving medication essential to the management of diabetes, a chronic condition that affection millions of Americans. The cost of insulin has risen dramatically in the last decade, however. A report by the Health Care Cost Institute reveals that the average price of insulin doubled from 2012 to 2016—making it difficult for many people to afford. More recently in 2019, the average price of insulin had reached $300 per vial (many people with diabetes require multiple vials of insulin every month). Therefore, insulin prices in the U.S. has emerged as a topic of controversy and great concern in recent years.  

The average price in the U.S., across all types of insulin, has been revealed to be more than ten times higher than the average price in every other country of the world. In fact, the closest any country has come, reportedly, to paying the $98.70 United States average was the $21.48 average in Chile (1). With millions of Americans struggling to afford basic household needs in the wake of COVID-19, these prices have only decreased by 5% between 2020 and 2021 (2). 

One report on this crisis shared the tragic story of a young man who was first diagnosed with type 1 diabetes at the age of 23 while working as a restaurant manager in Minnesota. By the age of 26, he was no longer eligible to remain on his mother’s health care insurance plan. The health insurance he qualified for came with a $7,600 deductible and a monthly premium of $440, which was beyond reach financially, leading to his decision to forego insurance and purchase insulin out of pocket. He attempted to ration his insulin due to financial constraints and was eventually found dead as a result of diabetic ketoacidosis (3).  

High insulin prices in the U.S. are caused by several factors. First, there is a lack of price regulation in the pharmaceutical industry, thereby allowing drug manufacturers to set their own prices. Second, the insulin market is very complex, involving multiple intermediaries such as wholesalers, insurers, and pharmacy benefit managers, each of which adds to the final cost of insulin. Finally, inconsistent insurance coverage, for insulin and health care in general, can exacerbate the situation (4). 

The exorbitant cost of insulin has fuelled widespread public anger and calls for reform. Certain advocates push for tighter regulation of medication prices, while others suggest alternative solutions, such as the development of generic versions of the medication or the importation of insulin from other countries into the U.S. 

In an attempt to reduce some of the burden, some initiatives try to help people patients with diabetes gain access to affordable insulin. Certain pharmaceutical companies offer patient assistance programs ensuring free or reduced-cost insulin to eligible individuals, for example, while some states have passed laws capping the cost of insulin or requiring insurers to cover the medication at no cost to patients. 

While the Biden administration, states, insurers, and insulin manufacturers have made efforts to cut insulin prices, Food and Drug Administration (FDA) approvals of biosimilars and generics have been the greatest drivers in the decrease in insulin prices in the U.S. (2). 

In the future, additional work remains to be done to continue to continue to drive insulin costs down and ensure basic health care access to all Americans.   

References  

1. The Astronomical Price of Insulin Hurts American Families | RAND [Internet]. [cited 2023 Mar 16]. Available from: https://www.rand.org/blog/rand-review/2021/01/the-astronomical-price-of-insulin-hurts-american-families.html 

2. How Much Does Insulin Cost? Here’s How 28 Brands and Generics Compare – GoodRx [Internet]. [cited 2023 Mar 16]. Available from: https://www.goodrx.com/healthcare-access/research/how-much-does-insulin-cost-compare-brands 

3. Rajkumar SV. The High Cost of Insulin in the United States: An Urgent Call to Action. Mayo Clin Proc. 2020 Jan 1;95(1):22–8. https://doi.org/10.1016/j.mayocp.2019.11.013 

4. Cefalu WT, Dawes DE, Gavlak G, Goldman D, Herman WH, Van Nuys K, et al. Insulin access and affordability working group: Conclusions and recommendations. Diabetes Care. 2018. doi: 10.2337/dci18-0019 

With a growing deficit and an economic recession on the horizon, Congress is searching for solutions to save government funding. Its recent decisions on where to trim down will, according to many in healthcare, come at the expense of patients and healthcare workers. Buried in the year-end omnibus legislation proposed to keep the government afloat until September 2023 was a policy that placed cuts on Medicare payment to physicians (1). These payments, remitted to physicians for treating patients with Medicare insurance plans, follow a strict schedule set by the Centers for Medicare and Medicaid Services (CMS), a department of the federal government. Although the omnibus extended Medicare coverage in United States territories and kept funding for telehealth services, other aspects of the bill have less positive implications for Medicare, which could negatively affect patient care (2).  

While the bill was initially designed to slash Medicare physician payments by 8.5%, a campaign by hundreds of physician organizations, including the American Medical Association (AMA), and a bipartisan effort of 45 Senators helped reduce the proposed cut to 2% in 2023, and at least 1.25% in 2024 (3). However, this reduction isn’t as much of a win as physicians had hoped. The decrease follows twenty years of flat payment rates, which translates to a decrease of 22% between 2001 and 2021 after adjusting for inflation (1). Additionally, the omnibus also reduced the Medicare physician incentive from 5% to 3.3% (3). However, Medicare’s Advanced Alternative Payment model, a system enacted by the American Rescue Plan Act in 2016, remains in place for the next two years, with a reduced incentive of 3.5% for qualified physicians (3). 

Physicians argue that the Medicare payment cuts will significantly impact patient care (4). Opponents of the decision argue that the reductions will result in subpar care due to the decrease in the Medicare incentive. Furthermore, many independent physician firms already report struggling with inflation and rising practice costs — therefore, the Medicare payment reduction presents yet another financial problem for many (5). In response, many practitioners may no longer treat Medicare patients, which may prompt them to stop accepting Medicare or close their practices (5). The decline in physicians who accept Medicare may become a significant problem for the 58 million Americans with this insurance plan (6).  

To combat these pay cuts, physician organizations around the country are pushing for Congress to change the Medicare payment system (7). Major organizations such as the California Medical Association have demanded Congress to implement an automatic inflation update, a key component that could eliminate the effective pay cuts due to the previous lack of consideration of inflation (7). Additionally, the decrease in the incentive payment is set to expire after one year, and physician organizations are planning on fighting to ensure it is not ratified in future legislation (7). More than 120 medical organizations have worked together with the American Medical Association to build a shared interpretation of their ideal payment system to implement in the future. While implementing these changes in a famously “broken” system will be an uphill battle, policymakers agree that the current system is unsustainable and that changes are necessary to provide quality health care to Medicare patients (1, 4, 8).  

References 

1: O’Reilly, K. 2022. “Medicare physician pay cuts underscore need to fix broken system.” American Medical Association. URL: https://www.ama-assn.org/practice-management/medicare-medicaid/medicare-physician-pay-cuts-underscore-need-fix-broken-system.  

2: Iroku-Malize, T. 2023. “Spending bill delivers AAFP advocacy wins, limits pay cut.” American Academy of Family Physicians. URL: https://www.aafp.org/news/blogs/wordfrompresident/entry/2023-funding-package-wins.html.  

3: Dyrda, L. 2022. “Congress keeps 2% Medicare physician pay cuts in 2023 spending bill.” Becker’s Hospital Review. URL: https://www.beckershospitalreview.com/hospital-physician-relationships/congress-keeps-2-medicare-physician-pay-cuts-in-2023-spending-bill.html.  

4: McAuliff, M. 2022. “Medicare pay cuts will hurt seniors’ care, doctors argue.” Kaiser Family Foundation. URL: https://khn.org/news/article/medicare-pay-cuts-will-hurt-seniors-care-doctors-argue/. 

5: American Medical Association. 2022. “Medicare updates compared to inflation (2001-2021).” American Medical Association. URL: https://www.ama-assn.org/system/files/ama-medicare-gaps-chart-grassroots-insert.pdf.   

6: Freed, M., Biniek, J., Damico, A. and Neuman, T. 2022. “Medicare Advantage in 2022: enrollment update and key trends.” Kaiser Family Foundation. URL: https://www.kff.org/medicare/issue-brief/medicare-advantage-in-2022-enrollment-update-and-key-trends/.  

7: California Medical Association. 2022. “Physicians react to Congress’ vote to cut Medicare payments by 2% in 2023.” California Medical Association. URL: https://www.cmadocs.org/newsroom/news/view/ArticleId/49991/Physicians-react-to-Congress-plan-to-cut-Medicare-payments-by-2-5-in-2023. 

8: Lubell, J. 2022. “Put a stop to ‘Groundhog Day’ games on Medicare physician pay.” American Medical Association. URL: https://www.ama-assn.org/practice-management/medicare-medicaid/put-stop-groundhog-day-games-medicare-physician-pay.   

In the United States, most routine gastrointestinal endoscopic procedures are performed with some form of sedation [1]. Endoscopy, which includes colonoscopy and esophagogastroduodenoscopy (EGD), is an uncomfortable procedure and can often cause abdominal pain, cramping, bloating, gagging, retching, and choking [2]. Using sedation for endoscopy not only allows for relaxation and an easier procedure, but also increases patient satisfaction with the procedure and outcome.   

Different forms and levels of sedation exist. Per the American Society of Anesthesiology (ASA) there is minimal, moderate, and deep sedation, as well as general anesthesia [4]. For endoscopic procedures, moderate sedation, in which the patient continues to be conscious and breathe on their own, is sufficient for endoscopy. Deep sedation with monitored anesthesia care and possible airway support can also be used. In rare cases, depending on patient comorbidities and complexity of the procedure, general anesthesia may be used with airway intubation. With moderate sedation, a variety of medications may be used, including benzodiazepines, opiates, and propofol. Agents such as midazolam, diazepam, pethidine, fentanyl, remifentanil, or meperidine are most typical. Midazolam and fentanyl have been found to be the most effective for endoscopy and have low cardiopulmonary complication rates [5].  

Patient satisfaction is an important outcome measure for procedures such as endoscopy, which is both a common diagnostic procedure and preventative procedure for colorectal cancer screening, and thus should be considered when deciding whether to provide sedation. Patients who are satisfied with care are more likely to comply with medical services and providers [6]. Studies have shown that conscious sedation endoscopy not only improves patient satisfaction, but also reduces fear and discomfort and improves compliance with repeat endoscopic procedures [3,7]. 

As sedated endoscopy has become more commonplace in clinical medicine, the quality of sedation becomes an important factor in patient outcomes. Midazolam, as aforementioned, has become the most widely used drug for endoscopy sedation. A recent study found that over 80% of all patients undergoing EGDs with midazolam sedation were satisfied with their experience [7]. Factors that influenced decreased patient satisfaction were procedure-related factors rather than sedation-related. In a similar study, patient satisfaction with endoscopic procedures was associated with the manner of endoscopy unit staff, length of time that staff devoted to explaining the procedure, environment of the endoscopy suite, and pain control during the procedure [6]. Thus, areas for improvement in endoscopy should be centered around the procedure itself and the environment. This includes inter-procedure waiting times, if a patient is undergoing a same day EGD and colonoscopy, and overall length of procedure time.   

Overall, there are high patient satisfaction rates with endoscopy with sedation and facilities should continue to focus on patient comfort by improving procedure wait times as well as environmental factors including patient comfort and staff mannerisms.  

References 

1. Lin, Otto S. “Sedation for Routine Gastrointestinal Endoscopic Procedures: A Review on Efficacy, Safety, Efficiency, Cost and Satisfaction.” Intestinal Research, vol. 15, no. 4, 2017, p. 456, dx.doi.org/10.5217%2Fir.2017.15.4.456, 10.5217/ir.2017.15.4.456. 

2. Ghanouni, Alex, et al. “Patients’ Experience of Colonoscopy in the English Bowel Cancer Screening Programme.” Endoscopy, vol. 48, no. 03, 3 Feb. 2016, pp. 232–240, 10.1055/s-0042-100613.  

3. Cohen, Lawrence B., et al. “Endoscopic Sedation in the United States: Results from a Nationwide Survey.” The American Journal of Gastroenterology, vol. 101, no. 5, May 2006, pp. 967–974, 10.1111/j.1572-0241.2006.00500.x.  

4. Gross, Jeffrey B, et al. “Practice Guidelines for the Perioperative Management of Patients with Obstructive Sleep Apnea.” Anesthesiology, vol. 104, no. 5, May 2006, pp. 1081–1093, 10.1097/00000542-200605000-00026. 

5. McQuaid, Kenneth R., and Loren Laine. “A Systematic Review and Meta-Analysis of Randomized, Controlled Trials of Moderate Sedation for Routine Endoscopic Procedures.” Gastrointestinal Endoscopy, vol. 67, no. 6, May 2008, pp. 910–923, 10.1016/j.gie.2007.12.046.  

6. Loftus, Russell, et al. “Patient Satisfaction with the Endoscopy Experience and Willingness to Return in a Central Canadian Health Region.” Canadian Journal of Gastroenterology, vol. 27, no. 5, 2013, pp. 259–266, 10.1155/2013/615206.  

7. Jin, Eun Hyo, et al. “How to Improve Patient Satisfaction during Midazolam Sedation for Gastrointestinal Endoscopy?” World Journal of Gastroenterology, vol. 23, no. 6, 2017, p. 1098, 10.3748/wjg.v23.i6.1098.  

The clinical introduction of antibiotics was one of the most important medical achievements of the twentieth century.⁴ In addition to preventing and fighting bacterial infections, antibiotics have permitted doctors to treat cancer, transplant organs, and perform open-heart surgery, among other procedures.⁴ Another lifesaving resource in modern medicine is antivirals, which are capable of preventing and fighting viral infections. These two classes of medications are distinct, though the conditions for which they are used often have similar symptoms. Increasing understanding of the differences between antibiotics vs. antivirals is also an important public health goal. 

The earliest antibiotics were traditional poultices from moldy bread used to treat open wounds in Serbia, China, Greece, and Egypt. ⁴ Antibiotics are among the most widely used pharmaceuticals in the world, with more than 250 antibiotics approved for human and animal medicine to kill or inhibit the growth of various bacteria.¹² Antibiotics are chemical compounds derived from natural, semi-natural or synthetic sources. ¹² These compounds can be separated into broad groups based on their chemical structure, the scope of their activities, and the mechanism by which they kill bacteria.¹² According to their chemical makeup, antibiotics can be classified into the following groups: lactams, macrolides, fluoroquinolones, tetracyclines, and sulfonamides.¹² The spectrum of activity of antibiotics is also divided into three classes: narrow-spectrum, broad-spectrum, and extended-spectrum.¹² Additionally, antibiotics are categorized based on their work, including the ability to kill bacteria and inhibit their growth.¹² 

Viruses are among the top of the World Health Organization’s current list of ten global health threats.¹¹ These complex organisms have caused millions of deaths globally throughout human history.⁵ Antivirals, a specialized class of pharmaceuticals, are one of the fascinating aspects of virology since they have successfully leveraged basic science to generate very effective therapeutics for many severe viral infections.^5,9 These medications are divided into two categories based on their mechanism of action: those that stimulate the immune system to fight viruses and those that attack viruses directly.⁵ Antiviral therapies’ potential effectiveness is greatly influenced by the pathogenesis, transmission, and epidemiological features of the virus.⁹ Viruses with a relatively short incubation period and generation time, as well as a quick rate of transmission, tend to be poor candidates for antiviral treatment because timely diagnosis and initiation of therapy is challenging.⁹ When comparing antibiotics vs. antivirals, the two types of medication have some similar strategies and limitations at a high level but differ greatly in their targets and their specific mechanisms. 

Despite advancements in technology and improvements in quality assurance, only a limited number of novel antiviral medications have been developed. ⁸ However, it is essential to highlight that the development of pharmaceutical drugs is a complex, multi-stage process that includes target identification and screening, lead generation and optimization, clinical trials, and drug registration with the FDA.⁷ Current antiviral medications and vaccines are ineffective against new and recurring viral infections.⁵ Finding therapeutic targets that inhibit the virus without harming the host’s cells is challenging.⁵ Long-term usage might result in unpleasant side effects such as gastrointestinal difficulties, exhaustion, headaches, neuropathy, and liver damage.¹ Furthermore, viruses, particularly RNA viruses, have rapidly acquired resistance to existing antiviral therapy due to their immense genetic variety.¹⁰ Since antivirals are the only therapeutic technique capable of breaking the viral replication cycle, newer antiviral treatments must be developed to fight this issue.^5,9  

Resistance to therapy has also been observed with antibiotics.⁶ The need for novel antibacterial medications to multidrug-resistant (MDR) bacterial infections is a significant global health concern, notably acknowledged by many global health officials across numerous organizations.² Developing novel antibacterial therapeutics that are effective against MDR is challenging due to difficulties in producing products with promising pharmacokinetics and pharmacodynamics qualities and acceptable toxicity profiles.² The problem of drug resistance is exacerbated by improper use of antibiotics vs. antivirals in place of the other, whether due to clinical uncertainty, misdiagnosis, or insufficient training. 

References 

1. “Antivirals: Antiviral Medication, What They Treat & How They Work.” Cleveland Clinic, https://my.clevelandclinic.org/health/drugs/21531-antivirals.  

2. Butler, M. S., Gigante, V., Sati, H., Paulin, S., Al-Sulaiman, L., Rex, J. H., Fernandes, P., Arias, C. A., Paul, M., Thwaites, G. E., Czaplewski, L., Alm, R. A., Lienhardt, C., Spigelman, M., Silver, L. L., Ohmagari, N., Kozlov, R., Harbarth, S., & Beyer, P. (2022). Analysis of the Clinical Pipeline of Treatments for Drug-Resistant Bacterial Infections: Despite Progress, More Action Is Needed. Antimicrobial agents and chemotherapy, 66(3), e0199121. https://doi.org/10.1128/AAC.01991-21 

3. Frieri, M., Kumar, K., & Boutin, A. (2017). Antibiotic resistance. Journal of infection and public health, 10(4), 369–378. https://doi.org/10.1016/j.jiph.2016.08.007 

4. Hutchings, M. I., Truman, A. W., & Wilkinson, B. (2019). Antibiotics: past, present and future. Current opinion in microbiology, 51, 72–80. https://doi.org/10.1016/j.mib.2019.10.008 

5. Kausar, S., Said Khan, F., Ishaq Mujeeb Ur Rehman, M., Akram, M., Riaz, M., Rasool, G., Hamid Khan, A., Saleem, I., Shamim, S., & Malik, A. (2021). A review: Mechanism of action of antiviral drugs. International journal of immunopathology and pharmacology, 35, 20587384211002621. https://doi.org/10.1177/20587384211002621 

6. Laws, M., Shaaban, A., & Rahman, K. M. (2019). Antibiotic resistance breakers: current approaches and future directions. FEMS microbiology reviews, 43(5), 490–516. https://doi.org/10.1093/femsre/fuz014Richman, D. D., & Nathanson, N. (2016). Antiviral Therapy. Viral Pathogenesis, 271–287. https://doi.org/10.1016/B978-0-12-800964-2.00020-3 

7. Mohs, R. C., & Greig, N. H. (2017). Drug discovery and development: Role of basic biological research. Alzheimer’s & dementia (New York, N. Y.), 3(4), 651–657. https://doi.org/10.1016/j.trci.2017.10.005 

8. Monto, A. S. (2006). Vaccines and Antiviral Drugs in Pandemic Preparedness. Emerging Infectious Diseases, 12(1), 55-60. https://doi.org/10.3201/eid1201.051068 

9. Richman, D. D., & Nathanson, N. (2016). Antiviral Therapy. Viral Pathogenesis, 271–287. https://doi.org/10.1016/B978-0-12-800964-2.00020-3 

10. Vere Hodge, A., & Field, H. J. (2011). General Mechanisms of Antiviral Resistance. Genetics and Evolution of Infectious Disease, 339–362. https://doi.org/10.1016/B978-0-12-384890-1.00013-3 

11. World Health Organization. Ten Health Issues Who Will Tackle This Year, World Health Organization, https://www.who.int/news-room/spotlight/ten-threats-to-global-health-in-2019.  

12. Yang, Q., Gao, Y., Ke, J., Show, P. L., Ge, Y., Liu, Y., Guo, R., & Chen, J. (2021). Antibiotics: An overview on the environmental occurrence, toxicity, degradation, and removal methods. Bioengineered, 12(1), 7376–7416. https://doi.org/10.1080/21655979.2021.1974657 

As of November 2022, more than 80% of the adult population in the United States had received at least one COVID-19 vaccine [1]. Although a large portion of the population is vaccinated, and vaccines are highly effective at preventing severe disease, public health experts continue to encourage greater uptake, as well as receiving boosters when applicable, as SARS-CoV-2 continues to circulate and affect the world [3, 4]. This article will discuss the status of populations who are still unvaccinated nearly three years into the pandemic. 

Rather than being united by a common set of values, there are two main unvaccinated populations in the US [4]. The first consists of people who are typically Christian, politically conservative, and white, and who live in rural areas [4]. This group is characterized by an adamant refusal to receive the vaccination [4]. Conversely, the other group – which contains more Hispanic and Black Americans, as well as Democrats compared to the first – is not so concretely opposed to vaccination [4]. Instead, they claim to be weighing their options and could be open to receiving them in due time [4]. The latter population reflects the minority of unvaccinated Americans, which means that most unvaccinated people are resistant to persuasion [4]. 

Many unvaccinated people express skepticism at the efficacy of COVID-19 vaccines, but reputable studies have documented the significant benefits of these treatments. For one, vaccination substantially reduces the likelihood that people will die from contracting COVID-19. According to a Scientific American article published in June 2022, for every 100,000 COVID-19 infections, 0.22 vaccinated people will die, compared with 1.71 unvaccinated people – more than a seven-fold difference [5]. Hospitalizations are also dramatically higher among the unvaccinated population: Unvaccinated people may be anywhere from 3.5 times to 17.7 times more likely to need to go to the hospital following SARS-CoV-2 infection [2]. 

Not only are unvaccinated adults more likely to suffer serious consequences as a result of COVID-19, but children can also benefit hugely from vaccinationn. A study by Olson et al. assessed how effective the Pfizer-BioNTech vaccine is at safeguarding people aged 12 to 17 from severe cases of COVID-19 [6]. The researchers found that the vaccine was 98% effective at avoiding life support care and intensive care unit internment, and 94% effective at avoiding hospitalization [6]. Seven adolescents died during the observed period, and all of them were not fully vaccinated [6]. Infants are among those who are especially vulnerable to infection. A study found that, of all the cases of severe COVID-19 in children observed across 50 hospitals, 20% involved infants [7]. While none of the infants in the study experienced significant complications, they did exhibit respiratory symptoms [7]. The researchers concluded that vaccination could help reduce this high rate [7]; in June 2022, the FDA gave emergency use authorization to two vaccines for children down to 6 months of age. 

One way to improve the status of unvaccinated populations is by disseminating information about vaccination and making the vaccine easier to receive. The CDC recommends targeting places such as workplaces and schools, where positive vaccination experiences can be shared, and information can be distributed through educational materials [8]. Moreover, employers can facilitate the process by compensating employees for the time they take to receive a vaccine, covering transportation costs, or even offering vaccinations at work [8]. If employers are hesitant to adopt these measures, community-based approaches, such as encouraging interactions with local medical professionals, may also work [8]. 

Of course, the likelihood of changing the minds of all unvaccinated people is unlikely. As such, alternative methods, like regular screening for SARS-CoV-2 infection, could help contain the disease [2]. In the end, the incomplete vaccination coverage demonstrates society’s need for adaptable policies, as the end of the COVID-19 pandemic appears impossible without public cooperation. Continuous effects to monitor the status of unvaccinated populations and implement new strategies as needed are also important. 

References 

[1] CDC, “COVID-19 Vaccinations in the United States,” CDC, Updated November 23, 2022. [Online]. Available: https://covid.cdc.gov/covid-data-tracker/#vaccinations_vacc-people-booster-percent-pop5.  

[2] F. P. Havers et al., “COVID-19-Associated Hospitalizations Among Vaccinated and Unvaccinated Adults 18 Years or Older in 13 US States, January 2021 to April 2022,” JAMA Internal Medicine, Updated September 8, 2022. [Online]. Available: https://doi.org/10.1001/jamainternmed.2022.4299. 

[3] K. M. Bubar et al., “SARS-CoV-2 transmission and impacts of unvaccinated-only screening in populations of mixed vaccination status,” Nature Communications, vol. 13, no. 2777, May 2022. [Online]. Available: https://doi.org/10.1073/pnas.2114279118. 

[4]  J. Bosman et al., “Who Are the Unvaccinated in America? There’s No One Answer,” The New York Times, Updated October 24, 2021. [Online]. Available: https://www.nytimes.com/2021/07/31/us/virus-unvaccinated-americans.html. 

[5]  A. Montañez and T. Lewis, “How to Compare COVID Deaths for Vaccinated and Unvaccinated People,” Scientific American, Updated June 7, 2022. [Online]. Available: https://www.scientificamerican.com/article/how-to-compare-covid-deaths-for-vaccinated-and-unvaccinated-people/. 

[6] S. M. Olson et al., “Effectiveness of BNT162b2 Vaccine against Critical Covid-19 in Adolescents,” The New England Journal of Medicine, vol. 386, p. 713-723, February 2022. [Online]. Available: https://doi.org/10.1056/NEJMoa2117995. 

[7] C. V. Hobbs et al., “Frequency, Characteristics and Complications of COVID-19 in Hospitalized Infants,” Pediatric Infectious Diseases Journal, vol. 41, no. 3, March 2022. [Online]. Available: https://doi.org/10.1097/INF.0000000000003435. 

[8] CDC, “Ways to Help Increase COVID-19 Vaccinations,” CDC, Updated June 17, 2022. [Online]. Available: https://www.cdc.gov/vaccines/covid-19/health-departments/generate-vaccinations.html. 

Propofol is a sedative-hypnotic prescription medication widely used as an “induction agent” – the drug that causes loss of consciousness – for general anesthesia in major surgery (Wilson et al., 2010). When administered at lower doses, it is also used for “conscious sedation” of patients getting outpatient procedures at ambulatory surgery centers, putting people in a drowsy, semi-conscious state (Wehrwein, 2011). Since propofol suppresses breathing and lowers blood pressure like other sedating anesthetics, the breathing and heart functions of patients must be monitored constantly (Wehrwein, 2011). Among anesthesiology professionals, propofol has become the “induction agent of choice,” especially because the traditional agent (a barbiturate called sodium thiopental) is no longer available (Wehrwein, 2011). The U.S. Drug Enforcement Administration does not list propofol as a controlled substance, in part because it is not associated with physical dependency (Wilson et al., 2010). Consequently, the drug’s addictive potential has received little attention. Even so, the risk of propofol abuse and addiction among the general population has been highlighted in studies worldwide (Xiong et al., 2018; Kim et al., 2015). 

In a review article published in 2010, three doctors in the Division of Emergency Medicine at the University of Utah cited pharmacological and experiential evidence to support propofol’s abuse potential (Wilson et al., 2010). The authors noted that volunteers in experimental studies described the drug’s effects “as a high or like being drunk,” and cited case reports that detailed “instances of sexual disinhibition” (Wilson et al., 2010; Wehrwein, 2011). As with other drugs of abuse, the pleasant feelings induced by propofol “can increase its risk for recreational use as well as addiction” (Kim et al., 2015). The review also mentioned that individuals can develop a tolerance for propofol, which necessitates needing more of the drug to achieve the same effect (Wilson et al., 2010). In a study published in the Journal of Addiction Medicine in 2013, Earley et al. analyzed 22 cases of propofol addiction in healthcare providers treated at an addiction center between 1990 and 2010. They found a “25% increase in admissions reporting propofol use, in each semi-decade, in the treatment groups,” demonstrating a potential trend towards increasing incidence of propofol abuse. The study also found that a majority of those treated for abuse were nurses and doctors that had been working in anesthetic departments and had ready access to the drug (Earley et al., 2013). Finally, animal studies have also substantiated the addiction risk of propofol: Gatch et al. established a rat model of the psychoactive effect of sub-anesthetic doses of propofol and found that propofol produces stimulus like known drugs of abuse (Gatch et al., 2011); there is also growing evidence that propofol can be self-administered (LeSage et al., 2000; Wang et al., 2016). 

The death of pop music star Michael Jackson in 2009 shined a light on propofol abuse by the public, spurring an increase in research in the years that followed (Jeon, 2015; Wehrwein, 2011). Still, focus on the risk of propofol addiction remains in its preliminary stage, and the addictive characteristic of the drug remains up for debate among researchers. More clinical and experimental evidence could help determine addiction risk, while exploration into the modes of propofol addiction could help identify at-risk populations. 

References 

Earley, Paul H., and Torin Finver. “Addiction to Propofol: A Study of 22 Treatment Cases.” Journal of Addiction Medicine 7, no. 3 (June 2013): 169–76. https://doi.org/10.1097/ADM.0b013e3182872901. 

Gatch, Michael B., and Michael J. Forster. “Behavioral and Toxicological Effects of Propofol.” Behavioural Pharmacology 22, no. 7 (October 2011): 718–22. https://doi.org/10.1097/FBP.0b013e32834aff84. 

Jeon, Young-Tae. “Propofol as a Controlled Substance: Poison or Remedy.” Korean Journal of Anesthesiology 68, no. 6 (December 2015): 525–26. https://doi.org/10.4097/kjae.2015.68.6.525. 

Kim, Eun-Jung, Seon-Hwa Kim, Yang-Jin Hyun, Yeon-Keun Noh, Ho-Sang Jung, Soon-Young Han, Chan-hye Park, Byung Moon Choi, and Gyu-Jeong Noh. “Clinical and Psychological Characteristics of Propofol Abusers in Korea: A Survey of Propofol Abuse in 38, Non-Healthcare Professionals.” Korean Journal of Anesthesiology 68, no. 6 (December 2015): 586–93. https://doi.org/10.4097/kjae.2015.68.6.586. 

LeSage, M. G., D. Stafford, and J. R. Glowa. “Abuse Liability of the Anesthetic Propofol: Self-Administration of Propofol in Rats under Fixed-Ratio Schedules of Drug Delivery.” Psychopharmacology 153, no. 1 (December 2000): 148–54. https://doi.org/10.1007/s002130000430. 

Wang, Benfu, Xiaowei Yang, Anna Sun, Lanman Xu, Sicong Wang, Wenxuan Lin, Miaojun Lai, Huaqiang Zhu, Wenhua Zhou, and Qingquan Lian. “Extracellular Signal-Regulated Kinase in Nucleus Accumbens Mediates Propofol Self-Administration in Rats.” Neuroscience Bulletin 32, no. 6 (October 25, 2016): 531–37. https://doi.org/10.1007/s12264-016-0066-1. 

Wehrwein, Peter. “Propofol: The Drug That Killed Michael Jackson.” Harvard Health, November 7, 2011. https://www.health.harvard.edu/blog/propofol-the-drug-that-killed-michael-jackson-201111073772. 

Wilson, Courtney, Peter Canning, and E. Martin Caravati. “The Abuse Potential of Propofol.” Clinical Toxicology (Philadelphia, Pa.) 48, no. 3 (March 2010): 165–70. https://doi.org/10.3109/15563651003757954. 

Xiong, Ming, Nimisha Shiwalkar, Kavya Reddy, Peter Shin, and Alex Bekker. “Neurobiology of Propofol Addiction and Supportive Evidence: What Is the New Development?” Brain Sciences 8, no. 2 (February 22, 2018): 36. https://doi.org/10.3390/brainsci8020036.

According to a study conducted in 2020, at least 1.6% of anesthesiologists are likely to suffer from substance use disorder during their careers [1]. Alcohol, opioids, and anesthetics are some of the substances that these physicians abuse most often [1]. Were substance use disorder considered an occupational hazard, anesthesiologists would rank among the most endangered workers in the United States [1]. 

Notwithstanding an individual’s profession, substance use disorder exposes its sufferers to severe risks. It is particularly dangerous for anesthesiologists, given the responsibility that they wield over the lives and health of other people [2]. Substance use disorder can impede an anesthesiologist’s training and result in severe professional consequences, such as failure to become certified in a subspecialty or to complete residency [2]. With the trajectory of anesthesiologists’ own lives – as well as the lives of others – in danger, the importance of curbing substance use disorder among them cannot be understated.  

Different types of policies serve to address this problem, with varying degrees of success. For instance, educational programs have been created to educate anesthesiologists about how to identify the disorder and intervene when they recognize it in their peers [2]. Identification can be difficult, given how anesthesiologists are cognizant of the signs of substance use disorder and thus more aware of how to hide them from others [3]. A pivotal warning sign to look out for is a change in the suspected individual’s functional capacity: substance abuse impedes people’s ability to carry out certain duties [3].  

Other warning signs are the replacement of a syringe or ampule’s contents with saline and the taking of narcotics from disposal containers [3]. Anesthesiologists with substance use disorder may also report that a case is opioid-based but then only administer beta-blockers and inhalational agents to the patient, taking the opioid medication for their own use [3]. To prevent these actions, some medical facilities conduct regular inspections of dispenser transactions and anesthetic records [2]. Meanwhile, to combat the removal of substances from waste, greater security measures may be wise. 

A more recent innovation has been the randomized substance testing of anesthesiologists, among other personnel, in medical institutions [2]. This strategy is not widely used – it appears to occur in a limited amount of civilian hospitals – but a study of anesthesiology residents at Massachusetts General Hospital suggests that it could be helpful in disincentivizing substance abuse and identifying it when it does occur [2, 4]. The experiment reported no cases of substance use over its 1,002-resident-year testing period, compared with four cases during the previous 719 resident years [4]. This was a limited study, however, so further research must occur to fully understand the beneficial effects of drug testing, if any, on substance use disorder among anesthesiologists and other physicians [4]. 

While submitting anesthesiologists to randomized testing may help identify those who suffer from substance abuse, the pathways to voluntary confession should also be improved to give physicians who wish to seek help an easy way to do so. It typically takes years for substance abuse to become apparent [5]. Giving anesthesiologists an option to disclose their disorder to a helpful, responsible authority could help challenge the stigma associated with the disorder and, ultimately, encourage anesthesiologists to openly seek help [6].  

Because of the incompleteness of current strategies, such as educational and surveillance programs, a multi-faceted approach that employs several of the aforementioned precautions may be the best way to address substance use disorder among anesthesiologists [2]. Through trial and error, medical institutions may be able to combat this problem and improve the health of their patients and their personnel. 

References 

[1] D. O. Warner et al., “Substance Use Disorder in Physicians after Completion of Training in Anesthesiology in the United States from 1977 to 2013,” Anesthesiology, vol. 133, p. 342-349, August 2020. [Online]. Available: https://doi.org/10.1097/ALN.0000000000003310. 

[2] E. O. Bryson, “The opioid epidemic and the current prevalence of substance use disorder in anesthesiologists,” Current Opinion in Anesthesiology, vol. 31, no. 3, p. 388-392, June 2018. [Online]. Available: https://doi.org/10.1097/ACO.0000000000000589. 

[3] L. G. Lefebvre and I. M. Kaufmann, “The identification and management of substance use disorders in anesthesiologists,” Canadian Journal of Anesthesia, vol. 64, p. 211-218, November 2016. [Online]. Available: https://doi.org/10.1007/s12630-016-0775-y. 

[4] M. G. Fitzsimons et al., “Reducing the Incidence of Substance Use Disorders in Anesthesiology Residents: 13 Years of Comprehensive Urine Drug Screening,” Anesthesiology, vol. 129, p. 821-828, October 2018. [Online]. Available: https://doi.org/10.1097/ALN.0000000000002348. 

[5] D. Volquind et al., “Occupational Hazards and Diseases Related to the Practice of Anesthesiology,” Brazilian Journal of Anesthesiology, vol. 63, no. 2, p. 227-232, March-April 2013. [Online]. Available: https://doi.org/10.1016/j.bjane.2012.06.006. 

[6] S. J. S. Bajwa and J. Kaur, “Risk and safety concerns in anesthesiology practice: The present perspective,” Anesthesia Essays and Researchers, vol. 6, no. 2, p. 227-232, March-April 2013. [Online]. Available: https://doi.org/10.1016/j.bjane.2012.06.006.

Ambulatory surgery centers (ASCs), modern healthcare facilities focused on providing same-day surgical care (including preventive and diagnostic procedures), have emerged as key players in ensuring safe, high quality, and cost-effective health care delivery ¹. Indeed, with a strong record of positive patient outcomes, they have reshaped the outpatient experience for millions of American patients by providing them with a convenient alternative to hospital-based procedures ². However, their safety and quality is important to monitor in order to ensure that patient outcomes are not negatively impacted. Several organizations, both public and private, provide safety and quality ratings for ASCs to this end.

Capitalizing on recent advances in surgical and pain management techniques, ASCs today regularly and safely perform most outpatient surgery procedures. In addition, since ASCs often specialize in certain specialties and/or procedures, they are able to place additional focus on patient experience and safety. In so doing, similar to hospital operating rooms, surgeons, nurses and medical professionals in ASCs adhere to a strict set of protocols  ³. 

The safety and quality of ASCs is ensured by close monitoring. Like hospitals, ASCs must abide by a number of laws and regulations. Most ASCs, for example, are Medicare-certified, and a large number are accredited by independent agencies that provide safety and quality ratings after a thorough screening and inspection process. 

In order to maintain a safe and sanitary environment, every ASC needs to establish and maintain procedures for preventing infections. The Centers for Disease Control (CDC) recommend contracting teams specializing in infection prevention ⁴ which can manage an ASC’s infection prevention program in a facility-tailored way. Meanwhile, individual ASCs may also utilize standardized surveys established to rate their own safety and implement changes accordingly ⁵. The national Agency for Healthcare Research and Quality (AHRQ), to this end, created the Ambulatory Surgery Center Survey on Patient Safety Culture. The survey is specifically designed for ASC staff, focusing on their own assessments of patient safety in their facility. 

Similarly, ASCs must conduct regular, comprehensive ratings of the safety and quality of care they provide to their patients. Today, both Medicare’s Ambulatory Surgical Center Quality Reporting (ASCQR) program and a program coordinated by the ASC Quality Collaboration (ASC QC) serve as robust, open-access ASC quality reporting programs ⁶. 

The ASC QC was created in 2006 as a cooperative effort between a number of different organizations in order to begin to develop standardized ASC quality measures ⁸, concentrating on both outcome and process measures. To date, nearly 2,000 ASCs have voluntarily participated in the reporting of its 11 distinct ASC performance measures.  

Administered by the Centers for Medicare and Medicaid Services (CMS), the ASCQR, in contrast, has been gathering data since 2012, focusing on 9 different performance areas ⁷. To date, nearly 97% of ASCs in the U.S., or over 5,000, collect and report performance measures to this program 

Both of these reporting programs continue to evolve, meanwhile, as a result of the ongoing cooperation and collaboration of ASC staff, government regulators, and independent rating agencies. 

Overall, ASCs offer safe and high-quality health care. However, as an increasing number of procedures shift from the hospital to the ASC, in-depth quality and safety assessments will be critical to maintaining such high standards into the future and across clinical contexts ⁹. 

References 

1. Grisel, J. & Arjmand, E. Comparing quality at an ambulatory surgery center and a hospital-based facility: Preliminary findings. Otolaryngol. – Head Neck Surg. (2009). doi:10.1016/j.otohns.2009.09.002 

2. What Is an ASC? – Advancing Surgical Care. Available at: https://www.advancingsurgicalcare.com/advancingsurgicalcare/asc/whatisanasc.

3. Quality of Care in ASCs – Advancing Surgical Care. Available at: https://www.advancingsurgicalcare.com/safetyquality/qualityofcareinascs.

4. for Disease Control, C. Guide to Infection Prevention For Outpatient Settings: Minimum Expectations for Safe Care. 

5. Ambulatory Surgery Center Survey on Patient Safety Culture | Agency for Healthcare Research and Quality. Available at: https://www.ahrq.gov/sops/surveys/asc/index.html.

6. ASC Quality Reporting – Advancing Surgical Care. Available at: https://www.advancingsurgicalcare.com/safetyquality/ascqualityreporting.

7. ASC Quality Reporting | CMS. Available at: https://www.cms.gov/Medicare/Quality-Initiatives-Patient-Assessment-Instruments/ASC-Quality-Reporting.

8. Welcome – ASC Quality Collaboration. Available at: https://www.ascquality.org/home.

9. Witiw, C. D., Wilson, J. R., Fehlings, M. G. & Traynelis, V. C. Ambulatory Surgical Centers: Improving Quality of Operative Spine Care? Glob. Spine J. (2020). doi:10.1177/2192568219849391 

Once labeled a “hidden killer,” malignant hyperthermia (MH) is a genetic skeletal muscle disorder that manifests as a hypermetabolic reaction in response to several anesthetic agents (1). Characterized by tachycardia, muscle rigidity, tachypnea, hypercarbia, rhabdomyolysis, metabolic acidosis, and hyperthermia that begin shortly after the induction of anesthesia, the condition can cause heart failure, renal failure, thromboses, and death (2). While the mortality rate for MH soared at 80% just decades ago, innovations in medicine and increased knowledge of the condition have slashed the rate to just 5% in recent years (3). The reaction occurs in roughly 1 in 5,000 to 50,000 patients receiving inhalational anesthetics — specifically sevoflurane, halothane, or desflurane — or the intravenous muscle relaxant succinylcholine; however, the genetic prevalence of the condition may be as high as 1 in 3,000 (1). Until recently, identifying susceptibility required laborious, expensive testing; currently, however, novel sequencing techniques enable medical teams to evaluate a patient’s risk for malignant hyperthermia and prepare accordingly. 

Although certain risk factors — including male sex, young age, and some neuromuscular disorders — were quickly linked to the condition, the genetic basis of MH remained unknown until 1991, when researchers discovered that the majority of MH cases were associated with heritable mutations in the ryanodine receptor 1 (RYR1) gene (4). While other genes play a role in MH, 50-70% of families with histories of the condition carry RYR1 mutations, thus rendering the gene a key diagnostic criterion (3, 4). The mutated gene encodes defective ryanodine receptor calcium channels in the sarcoplasmic reticula within muscle cells, predisposing the body to the hyperactive release of calcium cations, a cascade that causes the symptoms of MH when triggered by anesthetics (5). To identify the risk of MH, geneticists once performed in vitro contracture tests on biopsied muscle and analyzed patients’ personal and familial histories, but the former method requires extensive time and money and the latter often results in incomplete or inaccurate information. Next-generation sequencing (NGS), however, enables rapid, cost-effective identification of pathogenic RYR1 variants linked to malignant hyperthermia using only a blood sample (6). Importantly, NGS can look for and locate harmful variants in patients without personal or familial histories of MH, potentially saving the lives of these patients; however, the classification of the hundreds of RYR1 variants as pathogenic versus benign remains incomplete, indicating that in vitro testing and consideration of personal and familial history will persist in cases of unclassified mutations (6). 

While NGS must undergo improvements in the future, the method presents significant promise in preventing cases of MH and enabling the surgical team and anesthesia provider to prepare and identify MH when prevention is not an option. In addition to genetic sequencing, indications such as personal or familial history of malignant hyperthermia, rhabdomyolysis, or skeletal muscle disorders should cause medical professionals to categorize patients as susceptible to MH (6). For vulnerable patients, experts recommend opting for an intravenous anesthetic, such as propofol or etomidate, or administering prophylactic dantrolene sodium (7). Additionally, as a rising core temperature appears as one of the first symptoms of MH, experts recommend monitoring the core temperatures of patients undergoing anesthesia — indeed, the lack of this surveillance has been associated with a fourteen-fold increase in the risk of death (1). Finally, dantrolene sodium, the medication responsible for significantly decreasing deaths from MH, must be available and administered as soon as the condition is identified, as untreated MH carries a mortality rate of 70% (8). MH presents a critical issue for patients undergoing anesthesia, but technologies such as NGS and referral strategies have created ways to prevent morbidity and mortality from this lethal condition.  

References 

1: Rosenberg, H., Pollock, N., Schiemann, A., Bulger, T. and Stowell, K. (2015). Malignant hyperthermia: a review. Orphanet Journal of Rare Diseases, vol. 10. DOI: 10.1186/s13023-015-0310-1.  

2: Bin, X., Wang, B. and Tang, Z. (2021). Malignant hyperthermia: a killer if ignored. Journal of Perianesthesia Nursing, vol. 000, pp. 1-10. DOI: 10.1016/j.jopan.2021.08.018. 

3: Kim, J., Lee, C., Chung, C., Min, B. and Kim, D. (2022). Malignant hyperthermia: a case report with a literature review. Archives of Aesthetic Plastic Surgery, vol. 28, pp. 75-78. DOI: 10.14730/aaps.2022.00395.  

4: Robinson, R., Carpenter, D., Shaw, M., Halsall, J. and Hopkins, P. (2006). Mutations in RYR1 in malignant hyperthermia and central core disease. Human Mutation, vol. 27, pp. 977-989. DOI: 10.1002/humu.20356. 

5: Klingler, W., Heiderich, S., Girard, T., Gravino, E., Heffron, J., Johannsen, S., Jurkat-Rott, K., Ruffert, H., Schuster, F., Snoeck, M., Sorrentino, V., Tegazzin, V. and Legmann-Horn, F. (2014). 

Functional and genetic characterization of clinical malignant hyperthermia crises: a multi-centre study. Orphanet Journal of Rare Diseases, vol. 9, article no. 8. DOI: 10.1186/1750-1172-9-8.  

6: van den Bersselaar, L., Hellblom, A., Gashi, M., Kamsteeg, E., Voermans, N., Jungbluth, H., de Puydt, J., Heytens, L., Riazi, S. and Snoeck, M. (2022). Referral indications for malignant hyperthermia susceptibility diagnostics in patients without adverse anesthetic events in the era of next-generation sequencing. Anesthesiology, vol. 136, pp. 940-953. DOI: 10.1097/ALN.0000000000004199.  

7: Ruffert, H., Bastian, B., Bendixen, D., Girard, T., Heiderich, S., Hellblom, A., Hopkins, P., Johannsen, S., Snoeck, M., Urwyler, A. and Glahn, K. (2021). Consensus guidelines on perioperative management of malignant hyperthermia suspected or susceptible patients from the European Malignant Hyperthermia Group. British Journal of Anaesthesia, vol. 126, pp. 120-130. DOI: 10.1016/j.bja.2020.09.029.  

8: Collins, C. and Beirne, O. (2003). Concepts in the prevention and management of malignant hyperthermia. Journal of Oral and Maxillofacial Surgery, vol. 61, pp. 1340-1345. DOI: 10.1016/S0278-2391(03)00737-7.  

Every year, more than 230 million major surgeries occur [1]. Perioperative complications can be common, with major complications potentially occurring in as many as 20% of surgeries according to some data, irrespective of individual patient profiles and surgical discipline [2]. Not only can complications directly cause death during operations, but they are also associated with a higher rate of death after them [1]. Accordingly, perioperative complications are a major indicator of postoperative mortality. Despite the general acceptance of this fact among the medical community, the extent to which surgical complications affect postoperative mortality remains a point of ongoing investigation. 

Traditionally, healthcare systems, practitioners, and hospitals have relied on 30-day mortality as a measure of success following operations [2]. The association between surgical complications and 30-day mortality is well-documented. In 2005, Khuri and colleagues found that surgical complications were the “most important determinant of decreased postoperative survival” in the 30 days following an operation, based on data from a cohort of veteran patients who underwent major surgery [3]. The researchers focused on the 22 types of complications listed in the National Surgical Quality Improvement Program (NSQIP) [3]. These complications predicted mortality more accurately than intraoperative factors and preoperative patient risk, demonstrating the strength of the association [3]. 

Recent research indicates that a focus on only the first 30 days following surgery may fail to capture the strength of the connection between surgical complications and increased mortality [2]. A study conducted by Fowler et al. indicated that perioperative complications “cast a ‘long shadow’ of mortality beyond the 30-day time frame” [2]. Compared to patients who did not suffer complications, those who did experienced a nearly doubled risk of death in the 12-month postoperative period [2]. Indeed, more than 80% of the deaths among patients with complications occurred outside of the 30-day time frame, further demonstrating the limitations of this measure [2]. 

In response to similar evidence, researchers have proposed expanding the observation period to the first 60 or even 90 days following surgery [2]. While analyzing the data of 40,474 cancer surgery patients, Damhuis and colleagues found that the internationally recommended 30-day standard did capture most surgery-related deaths, contrary to the Fowler study [4]. However, a 90-day observation period allowed the researchers to identify more deaths, which may have been indirectly linked to surgery [4]. Consequently, the 90-day observation period, while not necessarily more informative for surgeons, can help patients make more informed decisions and, as such, is valuable. 

On the other hand, Hirji et al. published a study more in line with Fowler’s discoveries [5]. Their experiment centered on Medicare beneficiaries undergoing either transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) [5]. They considered 90-day mortality more “robustly informative” about patients’ first-year outcomes than 30-day mortality [5]. Additionally, it was more reliable as a measurement of hospital performance [5].  

All in all, it appears undeniable that complications increase postoperative mortality. By widening the postsurgical observation period, medical providers will have a more informed look into the link between surgical complications and postoperative success. 

References 

[1] R. M. Pearse et al., “Mortality after surgery in Europe: a 7 day cohort study,” The Lancet, vol. 380, no. 9847, p. 1059-1065, September 2012. [Online]. Available: DOI: 10.1016/S0140-6736(12)61148-9. 

[2] O. Stundner and P. S. Myles, “The ‘long shadow’ of perioperative complications: association with increased risk of death up to 1 year after surgery,” British Journal of Anaesthesia, vol. 35, no. 4, p. 410-417, April 2022. [Online]. Available: DOI: 10.1016/j.bja.2022.03.014. 

[3] S. F. Khuri et al., “Determinants of Long-Term Survival After Major Surgery and the Adverse Effect of Postoperative Complications,” Annals of Surgery, vol. 242, no. 3, p. 326-343, September 2005. [Online]. Available: DOI: 10.1097/01.sla.0000179621.33268.83. 

[4] R. Damhuis et al., “Comparison of 30-day, 90-day and in-hospital postoperative mortality for eight different cancer types,” British Journal of Surgery, vol. 99, no. 8, p. 1149-1154, August 2012. [Online]. Available: DOI: 10.1002/bjs.8813. 

[5] S. Hirji et al., “Utility of 90-Day Mortality vs 30-Day Mortality as a Quality Metric for Transcatheter and Surgical Aortic Valve Replacement Outcomes,” JAMA Cardiology, vol. 5, no. 2, p. 156-165, December 2019. [Online]. Available: DOI: 10.1001/jamacardio.2019.4657.