2 Minute Medicine Rewind May 25, 2020

Epidemiology, Clinical Course, and Outcomes of Critically Ill Adults With COVID-19 In New York City: A Prospective Cohort Study

1. COVID-19-positive adults were commonly found to have at least one comorbid condition, including hypertension and diabetes.

2. In-hospital mortality was independently associated with older age, chronic cardiac and pulmonary diseases, and elevated concentrations of interleukin-6 and D-dimer.

3. Critical illness is associated with elevated need for invasive mechanical ventilation, as well as extrapulmonary dysfunction.

Evidence Rating Level: 2 (Good)

As of April 28, 2020, more than 40,000 COVID-19 patients have been hospitalized in New York City. Given the ongoing and precarious nature of this pandemic, it is important to investigate the epidemiology, clinical course, and outcomes of patients who become critically ill due to COVID-19. This prospective observational cohort study, taking place at two hospitals affiliated with Columbia University Irving Medical Center identified adult, COVID-19-positive patients from March 2 to April 1, 2020 who were critically ill with acute hypoxemic respiratory failure to collect biomarker, clinical, and treatment data. A total of 1,150 adults with COVID-19 were admitted to the two hospitals (M [IQR] = 62 [51 to 72] years, 33% female), 22% of whom were critically ill. Approximately 82% of patients presented with at least one comorbid illness, with the most common being hypertension (63%), diabetes (36%), and obesity (46%). By April 28, 2020, 39% of the patients had passed away and 37% were still hospitalized. Of those who remained hospitalized, 79% required invasive mechanical ventilation (median [IQR] duration = 18 [9 to 28] days), 66% received vasopressors, and 31% received renal replacement therapy. In-hospital deterioration was found to have a median duration of 3 days (IQR 1 to 6 days). Increased in-hospital mortality was independently associated with older age (adjusted HR 1.31, 95% CI 1.09 to 1.57), chronic cardiac disease (adjusted HR 1.76, 95% CI 1.08 to 2.86), chronic pulmonary disease (adjusted HR 2.94, 95% CI 1.48 to 5.84), elevated concentrations of interleukin-6 (adjusted HR 1.11, 95% CI 1.02 to 1.20 per decile increase), and higher D-dimer concentrations (adjusted HR 1.10, 95% CI 1.01 to 1.19 per decile increase). Overall, this study aligns with those previously published while remaining specific to COVID-19 patients in New York City. Hypertension and diabetes are common comorbidities and mortality is associated with specific risk factors that should be considered as we learn more about how to control the spread of the virus.

Association Between Tumor Necrosis Factor Inhibitor Exposure and Inflammatory Central Nervous System Events

1. Tumor necrosis factor inhibitor exposure in patients with autoimmune disease, particularly rheumatoid arthritis, was associated with increased risk of inflammatory central nervous system events.

Evidence Rating Level: 2 (Good)

The U.S. Food and Drug Administration has approved five tumor necrosis factor (TNF) inhibitors as immunotherapies for autoimmune diseases: etanercept, adalimumab, infliximab, golimumab, and certolizumab pegol. However, TNF inhibitor exposure has since been found to potentially be associated with inflammatory, demyelinating events in the central nervous system (CNS) including but not limited to multiple sclerosis and optic neuritis. This nested case-control study investigated TNF inhibitors (type, cumulative exposure duration, time of exposure) and subsequent risk of demyelinating (n = 56) and nondemyelinating CNS events (n = 50) in individuals with autoimmune disease. Participants with autoimmune disease were selected via the Mayo Clinic electronic medical record system across three sites. Between 2003 and 2019. The control group (no CNS events) was selected from the same system and matched 1:1 for sex, birth year, and autoimmune disease (n = 106). Participants were excluded if any inflammatory CNS events occurred prior to the development of an autoimmune disease. Thus, a total of 212 participants were included in this study (median [IQR] age at disease onset = 52 [43-62] years, 64% female). A total of 48 participants with inflammatory demyelinating CNS events had multiple sclerosis, optic neuritis, transverse myelitis, or neuromyelitis optica spectrum disorder (NMOSD). Common demyelinating CNS events were meningitis, idiopathic leptomeningitis, idiopathic pachymeningitis, idiopathic meningoencephalitis, autoimmune encephalitis, neurosarcoidosis, and CNS vasculitis. The experimental group was more likely to experience TNF inhibitor exposure (difference 20%), suggesting an association with increased risk of inflammatory CNS events (adjusted OR 3.01, 95% CI 1.55 to 5.82, p = 0.001). Upon stratification by nondemyelinating and demyelinating events, results remained similar. Further analyses suggested a primary association among those with rheumatoid arthritis (adjusted OR 4.82, 95% CI 1.62 to 14.36, p = 0.005). Overall, this study supports the hypothesis that TNF exposure is associated with increased odds of inflammatory CNS events in individuals with autoimmune disease. Further research is warranted to determine when this increased risk is introduced and how to improve these outcomes.

Demographics, Substance Use Behaviors, and Clinical Characteristics of Adolescents With e-Cigarette, or Vaping, Product Use-Associated Lung Injury (EVALI) In the United States In 2019

1. Adolescents with e-cigarette, or vaping, product use–associated lung injury (EVALI) were more likely to report informal sources for obtaining nicotine- and THC-containing products than young adults and adults.

2. EVALI adolescents were more likely than young adults and adults to report a history of ADHD, asthma, and gastrointestinal issues.

Evidence Rating Level: 2 (Good)

As of mid-December 2019, states have reported a total of 2,506 hospitalized or deceased cases of e-cigarette or vaping product use-associated lung injury (EVALI). Due to limited available data on the clinical characteristics of adolescents with EVALI, this cross-sectional study sought to determine the unique differences between these adolescents and their adult counterparts. A total of 360 hospitalized or deceased adolescents (age range 13 to 17 years, 32.1% female), 859 young adults (age range 18 to 24 years, 27.6% female), and 936 adults (age range 25 to 49 years, 34.4% female) with EVALI were included in this study. Among the adolescent group, 81.7% reported using tetrahydrocannabinol (THC)-containing products, 62.4% reported any nicotine-containing product, and 50.8% reported using both product types. This group was also more likely to report informal sources for obtaining these products (96.5% THC, 50.5% nicotine) compared to both young adults (86.9% THC [adjusted PR 1.11, 95% CI 1.05 to 1.18; 19.8% nicotine [adjusted PR 2.49, 95% CI 1.78 to 3.46) and adults (75.1% THC [adjusted PR 1.29, 95% CI 1.19 to 1.40]); 24.3% nicotine [adjusted PR 2.06, 95% CI 1.49 to 2.84]). THC products have been found to be diluted by vitamin E acetate, an EVALI-associated chemical. Adolescents reported a 400% greater likelihood (18.1%) of a history of Attention-Deficit/Hyperactivity Disorder (ADHD) than adults (4.9%, adjusted PR 3.74, 95% CI 1.92 to 7.26). Asthma was also reported for frequently among adolescents than adults (adjusted PR 1.53, 95% CI 1.14 to 2.05). Lastly, gastrointestinal symptoms were more common among adolescents than adults (difference 19.2%, adjusted PR 1.20, 95% CI 1.13 to 1.28 vs adjusted PR 1.03, 95% CI 1.00 to 1.06, respectively). While data collection methods varied across jurisdictions, occasionally resulting in small sample sizes, and medical histories were self-reported, this study still holds value in describing unique characteristics of EVALI adolescents. It is important to consider factors such as ADHD and asthma in adolescents and educate on the risks posed by e-cigarette or vaping products.

Sociodemographic Factors Associated With High Risk for Firearm Suicide Among US Adults

1. Firearm suicide risk is elevated among those living in states with high firearm ownership, those living in rural areas, those with a military background, and those of white, non-Hispanic backgrounds.

Evidence Rating Level: 2 (Good)

Suicide is an ongoing pandemic and a leading cause of death in the U.S. The most common method among those who die by suicide is firearm (50.5%). However, limited information is known regarding the personal characteristics associated with firearm suicide risk. This retrospective cohort study examined respondents from the Mortality Disparities Across Communities study, which linked 2008-2015 National Death Index death records with 2008 American Community Survey data. Firearm suicide rates were found to be highest among those with military background (21.2 per 100,000 person-years), 95% CI 19.4 to 23.1). Other high-risk groups were disabled individuals (14.0 per 100,000 person-years, 95% CI 12.7 to 15.3), male gender (13.6 per 100,000 person-years, 95% CI 13.0 to 14.3), adults ≥ 65 years of age (11.8 per 100,000 person-years, 95% CI 10.7 to 13.0), rural residents (11.5 per 100,000 person-years, 95% CI 10.6 to 12.4), separated/divorced individuals (11.3 per 100,000 person-years, 95% CI 10.2 to 12.5), and adults in states with > 50% firearm ownership (11.5 per 100,000 person-years, 95% CI 9.5 to 13.7). U.S. firearm owners had a greater risk of firearm suicide (HR 3.00, 95% CI 2.50 to 4.39) and non-firearm suicide (HR 1.20, 95% CI 0.97 to 1.48) than noncitizens. Risk increased with combinations of these variables. For example, firearm suicide rates were higher among males in high firearm ownership states (19.9 per 100,000 person-years) than the same demographic in states with low firearm ownership (7.9 per 100,000 person-years). For females, firearm suicide rates were highest among those with a net income loss (5.5 per 100,000 person-years, 95% CI 3.2 to 9.0), those who were disabled, (3.8 per 100,000 person-years), and those in states with high firearm ownership (3.5 per 100,000 person-years, 95% CI 2.1 to 5.5). Overall, this study suggests that there are specific factors that should be considered when assessing for suicide risk in certain populations. This is particularly timely given the rise in gun ownership and mental health concerns during the COVID-19 pandemic.

Association Between Legal Performance-Enhancing Substances and Use of Anabolic-Androgenic Steroids In Young Adults

1. Young men who used legal performance-enhancing substances were more likely to engage in future anabolic-androgenic steroid use.

2. Compared to non-users, use of legal performance-enhancing substances among young adult males was associated with a three-fold increase in risk of future anabolic-androgenic steroid use.

3. No associations between these substance use activities were found among young women.

Evidence Rating Level: 2 (Good)

There is limited research investigating the longitudinal associations between legal performance-enhancing substances such as creatine monohydrate and later use of anabolic-androgenic steroids among young adults. Given that these schedule III drugs are frequently used without a valid prescription, this is an important area of study. This prospective cohort study of the National Longitudinal Study of Adolescent to Adult Health examined data of 12,695 young adults (mean [SE] age = 21.8 [0.1] years). Both waves III (ages 18 to 26 years) and IV (ages 24-32 years) were available among this sample. Use of legal performance-enhancing substances in wave III were observed in 16.1% of males and 1.2% of females. In wave IV, however, only 4.2% of men and 0.8% of women reported anabolic-androgenic steroid use during the previous year. Men who initially reported legal performance-enhancing substance use were more likely to transition to using anabolic-androgenic steroid use than those who did not use legal performance-enhancing substances (difference 9.8%, p<0.001). Compared to non-users, the male group that engaged in legal performance-enhancing substance use had higher odds of wave IV anabolic-androgenic steroid use (adjusted OR 3.18, 95% CI 1.90 to 5.32, p<0.001). There was no association between legal performance-enhancing substance use at wave III and anabolic-androgenic steroid use at wave IV among females (p = 0.14). Overall, this study highlights the importance of imposing regulations on performance-enhancing substances in vulnerable populations such as young adults, as this activity may graduate to more significant concerns related to a three-fold increase in odds of illicit steroid use.

Image: PD

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