Hospitalizations and Deaths Associated with EVALI.

BACKGROUND: As of January 7, 2020, a total of 2558 hospitalized patients with nonfatal cases and 60 patients with fatal cases of e-cigarette, or vaping, product use-associated lung injury (EVALI) had been reported to the Centers for Disease Control and Prevention (CDC). METHODS: In a national study, we compared the characteristics of patients with fatal cases of EVALI with those of patients with nonfatal cases to improve the ability of clinicians to identify patients at increased risk for death from the condition. Health departments reported cases of EVALI to the CDC and included, when available, data from medical-record abstractions and patient interviews. Analyses included all the patients with fatal or nonfatal cases of EVALI that were reported to the CDC as of January 7, 2020. We also present three case reports of patients who died from EVALI to illustrate the clinical characteristics common among such patients. RESULTS: Most of the patients with fatal or nonfatal cases of EVALI were male (32 of 60 [53%] and 1666 of 2498 [67%], respectively). The proportion of patients with fatal or nonfatal cases was higher among those who were non-Hispanic white (39 of 49 [80%] and 1104 of 1818 [61%], respectively) than among those in other race or ethnic groups. The proportion of patients with fatal cases was higher among those 35 years of age or older (44 of 60 [73%]) than among those younger than 35 years, but the proportion with nonfatal cases was lower among those 35 years of age or older (551 of 2514 [22%]). Among the patients who had an available medical history, a higher proportion of those with fatal cases than those with nonfatal cases had a history of asthma (13 of 57 [23%] vs. 102 of 1297 [8%]), cardiac disease (26 of 55 [47%] vs. 115 of 1169 [10%]), or a mental health condition (32 of 49 [65%] vs. 575 of 1398 [41%]). A total of 26 of 50 patients (52%) with fatal cases had obesity. Half the patients with fatal cases (25 of 54 [46%]) were seen in an outpatient setting before hospitalization or death. CONCLUSIONS: Chronic conditions, including cardiac and respiratory diseases and mental health conditions, were common among hospitalized patients with EVALI.

Vitamin E Acetate in Bronchoalveolar-Lavage Fluid Associated with EVALI.

BACKGROUND: The causative agents for the current national outbreak of electronic-cigarette, or vaping, product use-associated lung injury (EVALI) have not been established. Detection of toxicants in bronchoalveolar-lavage (BAL) fluid from patients with EVALI can provide direct information on exposure within the lung. METHODS: BAL fluids were collected from 51 patients with EVALI in 16 states and from 99 healthy participants who were part of an ongoing study of smoking involving nonsmokers, exclusive users of e-cigarettes or vaping products, and exclusive cigarette smokers that was initiated in 2015. Using the BAL fluid, we performed isotope dilution mass spectrometry to measure several priority toxicants: vitamin E acetate, plant oils, medium-chain triglyceride oil, coconut oil, petroleum distillates, and diluent terpenes. RESULTS: State and local health departments assigned EVALI case status as confirmed for 25 patients and as probable for 26 patients. Vitamin E acetate was identified in BAL fluid obtained from 48 of 51 case patients (94%) in 16 states but not in such fluid obtained from the healthy comparator group. No other priority toxicants were found in BAL fluid from the case patients or the comparator group, except for coconut oil and limonene, which were found in 1 patient each. Among the case patients for whom laboratory or epidemiologic data were available, 47 of 50 (94%) had detectable tetrahydrocannabinol (THC) or its metabolites in BAL fluid or had reported vaping THC products in the 90 days before the onset of illness. Nicotine or its metabolites were detected in 30 of 47 of the case patients (64%). CONCLUSIONS: Vitamin E acetate was associated with EVALI in a convenience sample of 51 patients in 16 states across the United States. (Funded by the National Cancer Institute and others.).

Validation of the Prevention Impacts Simulation Model (PRISM).

INTRODUCTION: Demonstrating the validity of a public health simulation model helps to establish confidence in the accuracy and usefulness of a model's results. In this study we evaluated the validity of the Prevention Impacts Simulation Model (PRISM), a system dynamics model that simulates health, mortality, and economic outcomes for the US population. PRISM primarily simulates outcomes related to cardiovascular disease but also includes outcomes related to other chronic diseases that share risk factors. PRISM is openly available through a web application. METHODS: We applied the model validation framework developed independently by the International Society of Pharmacoeconomics and Outcomes Research and the Society for Medical Decision Making modeling task force to validate PRISM. This framework included model review by external experts and quantitative data comparison by the study team. RESULTS: External expert review determined that PRISM is based on up-to-date science. One-way sensitivity analysis showed that no parameter affected results by more than 5%. Comparison with other published models, such as ModelHealth, showed that PRISM produces lower estimates of effects and cost savings. Comparison with surveillance data showed that projected model trends in risk factors and outcomes align closely with secular trends. Four measures did not align with surveillance data, and those were recalibrated. CONCLUSION: PRISM is a useful tool to simulate the potential effects and costs of public health interventions. Results of this validation should help assure health policy leaders that PRISM can help support community health program planning and evaluation efforts.

Potential Indirect Effects of the COVID-19 Pandemic on Use of Emergency Departments for Acute Life-Threatening Conditions - United States, January-May 2020.

On March 13, 2020, the United States declared a national emergency in response to the coronavirus disease 2019 (COVID-19) pandemic. Subsequently, states enacted stay-at-home orders to slow the spread of SARS-CoV-2, the virus that causes COVID-19, and reduce the burden on the U.S. health care system. CDC* and the Centers for Medicare & Medicaid Services (CMS)† recommended that health care systems prioritize urgent visits and delay elective care to mitigate the spread of COVID-19 in health care settings. By May 2020, national syndromic surveillance data found that emergency department (ED) visits had declined 42% during the early months of the pandemic (1). This report describes trends in ED visits for three acute life-threatening health conditions (myocardial infarction [MI, also known as heart attack], stroke, and hyperglycemic crisis), immediately before and after declaration of the COVID-19 pandemic as a national emergency. These conditions represent acute events that always necessitate immediate emergency care, even during a public health emergency such as the COVID-19 pandemic. In the 10 weeks following the emergency declaration (March 15-May 23, 2020), ED visits declined 23% for MI, 20% for stroke, and 10% for hyperglycemic crisis, compared with the preceding 10-week period (January 5-March 14, 2020). EDs play a critical role in diagnosing and treating life-threatening conditions that might result in serious disability or death. Persons experiencing signs or symptoms of serious illness, such as severe chest pain, sudden or partial loss of motor function, altered mental state, signs of extreme hyperglycemia, or other life-threatening issues, should seek immediate emergency care, regardless of the pandemic. Clear, frequent, highly visible communication from public health and health care professionals is needed to reinforce the importance of timely care for medical emergencies and to assure the public that EDs are implementing infection prevention and control guidelines that help ensure the safety of their patients and health care personnel.

Update: Characteristics of a Nationwide Outbreak of E-cigarette, or Vaping, Product Use-Associated Lung Injury - United States, August 2019-January 2020.

Since August 2019, CDC, the Food and Drug Administration (FDA), state and local health departments, and public health and clinical stakeholders have been investigating a nationwide outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) (1). This report updates patient demographic characteristics, self-reported substance use, and hospitalization dates for EVALI patients reported to CDC by states, as well as the distribution of emergency department (ED) visits related to e-cigarette, or vaping, products analyzed through the National Syndromic Surveillance Program (NSSP). As of January 14, 2020, a total of 2,668 hospitalized EVALI cases had been reported to CDC. Median patient age was 24 years, and 66% were male. Overall, 82% of EVALI patients reported using any tetrahydrocannabinol (THC)-containing e-cigarette, or vaping, product (including 33% with exclusive THC-containing product use), and 57% of EVALI patients reported using any nicotine-containing product (including 14% with exclusive nicotine-containing product use). Syndromic surveillance indicates that ED visits related to e-cigarette, or vaping, products continue to decline after sharply increasing in August 2019 and peaking in September 2019. Clinicians and public health practitioners should remain vigilant for new EVALI cases. CDC recommends that persons not use THC-containing e-cigarette, or vaping, products, especially those acquired from informal sources such as friends, family members, or from in-person or online dealers. Vitamin E acetate is strongly linked to the EVALI outbreak and should not be added to any e-cigarette, or vaping, products (2). However, evidence is not sufficient to rule out the contribution of other chemicals of concern, including chemicals in either THC- or non-THC-containing products, in some reported EVALI cases.

E-cigarette, or Vaping, Product Use-Associated Lung Injury: Looking Back, Moving Forward.

Implications In this commentary, we describe the evidence-based approach used to identify the primary cause of EVALI and to curb the 2019 outbreak. We also discuss future research opportunities and public health practice considerations to prevent a resurgence of EVALI.

Risk Factors for E-Cigarette, or Vaping, Product Use-Associated Lung Injury (EVALI) Among Adults Who Use E-Cigarette, or Vaping, Products - Illinois, July-October 2019.

The United States is experiencing an unprecedented outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) (1). All EVALI patients have used e-cigarette, or vaping, products, and most (≥85%) have reported using products containing tetrahydrocannabinol (THC) (2,3), the principal psychoactive component of cannabis. To examine whether e-cigarette, or vaping, product use behaviors differed between adult EVALI patients and adults who use these products but have not developed lung injury, the Illinois Department of Public Health (IDPH) conducted an online public survey during September-October 2019 targeting e-cigarette, or vaping, product users in Illinois. Among 4,631 survey respondents, 94% reported using any nicotine-containing e-cigarette, or vaping, products in the past 3 months; 21% used any THC-containing products; and 11% used both THC-containing products and nicotine-containing products. Prevalence of THC-containing product use was highest among survey respondents aged 18-24 years (36%) and decreased with increasing age. E-cigarette, or vaping, product use behaviors of 66 EVALI patients aged 18-44 years who were interviewed as part of the ongoing outbreak investigation were compared with a subset of 519 survey respondents aged 18-44 years who reported use of THC-containing e-cigarette, or vaping, products. Compared with these survey respondents, EVALI patients had higher odds of reporting exclusive use of THC-containing products (adjusted odds ratio [aOR] = 2.0, 95% confidence interval [CI] = 1.1-3.6); frequent use (more than five times per day) of these products (aOR = 3.1, 95% CI = 1.6-6.0), and obtaining these products from informal sources, such as a dealer, off the street, or from a friend (aOR = 9.2, 95% CI = 2.2-39.4). The odds of using Dank Vapes, a class of largely counterfeit THC-containing products, was also higher among EVALI patients (aOR = 8.5, 95% CI = 3.8-19.0). These findings reinforce current recommendations not to use e-cigarette, or vaping, products that contain THC and not to use any e-cigarette, or vaping, products obtained from informal sources. In addition, because the specific compound or ingredient causing lung injury is not yet known, CDC continues to recommend that persons consider refraining from use of all e-cigarette, or vaping, products while the outbreak investigation continues (1).

Characteristics of Hospitalized and Nonhospitalized Patients in a Nationwide Outbreak of E-cigarette, or Vaping, Product Use-Associated Lung Injury - United States, November 2019.

CDC, the Food and Drug Administration (FDA), state and local health departments, and public health and clinical stakeholders are investigating a nationwide outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) (1). As of November 13, 2019, 49 states, the District of Columbia, and two U.S. territories (Puerto Rico and U.S. Virgin Islands) have reported 2,172 EVALI cases to CDC, including 42 (1.9%) EVALI-associated deaths. To inform EVALI surveillance, including during the 2019-20 influenza season, case report information supplied by states for hospitalized and nonhospitalized patients with EVALI were analyzed using data collected as of November 5, 2019. Among 2,016 EVALI patients with available data on hospitalization status, 1,906 (95%) were hospitalized, and 110 (5%) were not hospitalized. Demographic characteristics of hospitalized and nonhospitalized patients were similar; most were male (68% of hospitalized versus 65% of nonhospitalized patients), and most were aged <35 years (78% of hospitalized versus 74% of nonhospitalized patients). These patients also reported similar use of tetrahydrocannabinol (THC)-containing products (83% of hospitalized versus 84% of nonhospitalized patients). Given the similarity between hospitalized and nonhospitalized EVALI patients, the potential for large numbers of respiratory infections during the emerging 2019-20 influenza season, and the potential difficulty in distinguishing EVALI from respiratory infections, CDC will no longer collect national data on nonhospitalized EVALI patients. Further collection of data on nonhospitalized patients will be at the discretion of individual state, local, and territorial health departments. Candidates for outpatient management of EVALI should have normal oxygen saturation (≥95% while breathing room air), no respiratory distress, no comorbidities that might compromise pulmonary reserve, reliable access to care, strong social support systems, and should be able to ensure follow-up within 24-48 hours of initial evaluation and to seek medical care promptly if respiratory symptoms worsen. Health care providers should emphasize the importance of annual influenza vaccination for all persons aged ≥6 months, including persons who use e-cigarette, or vaping, products (2,3).

Characteristics of a Multistate Outbreak of Lung Injury Associated with E-cigarette Use, or Vaping - United States, 2019.

Electronic cigarettes (e-cigarettes), also called vapes, e-hookas, vape pens, tank systems, mods, and electronic nicotine delivery systems (ENDS), are electronic devices that produce an aerosol by heating a liquid typically containing nicotine, flavorings, and other additives; users inhale this aerosol into their lungs (1). E-cigarettes also can be used to deliver tetrahydrocannabinol (THC), the principal psychoactive component of cannabis (1). Use of e-cigarettes is commonly called vaping. Lung injury associated with e-cigarette use, or vaping, has recently been reported in most states (2-4). CDC, the Food and Drug Administration (FDA), state and local health departments, and others are investigating this outbreak. This report provides data on patterns of the outbreak and characteristics of patients, including sex, age, and selected substances used in e-cigarette, or vaping, products reported to CDC as part of this ongoing multistate investigation. As of September 24, 2019, 46 state health departments and one territorial health department had reported 805 patients with cases of lung injury associated with use of e-cigarette, or vaping, products to CDC. Sixty-nine percent of patients were males, and the median age was 23 years (range = 13-72 years). To date, 12 deaths have been confirmed in 10 states. Among 514 patients with information on substances used in e-cigarettes, or vaping products, in the 30 days preceding symptom onset, 76.9% reported using THC-containing products, and 56.8% reported using nicotine-containing products; 36.0% reported exclusive use of THC-containing products, and 16.0% reported exclusive use of nicotine-containing products. The specific chemical exposure(s) causing the outbreak is currently unknown. While this investigation is ongoing, CDC recommends that persons consider refraining from using e-cigarette, or vaping, products, particularly those containing THC. CDC will continue to work in collaboration with FDA and state and local partners to investigate cases and advise and alert the public on the investigation as additional information becomes available.

Evaluation of Bronchoalveolar Lavage Fluid from Patients in an Outbreak of E-cigarette, or Vaping, Product Use-Associated Lung Injury - 10 States, August-October 2019.

CDC, the Food and Drug Administration (FDA), state and local health departments, and multiple public health and clinical partners are investigating a national outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI). Based on data collected as of October 15, 2019, 86% of 867 EVALI patients reported using tetrahydrocannabinol (THC)-containing products in the 3 months preceding symptom onset (1). Analyses of THC-containing product samples by FDA and state public health laboratories have identified potentially harmful constituents in these products, such as vitamin E acetate, medium chain triglyceride oil (MCT oil), and other lipids (2,3) (personal communication, D.T. Heitkemper, FDA Forensic Chemistry Center, November 2019). Vitamin E acetate, in particular, might be used as an additive in the production of e-cigarette, or vaping, products; it also can be used as a thickening agent in THC products (4). Inhalation of vitamin E acetate might impair lung function (5-7).

Update: Interim Guidance for Health Care Providers for Managing Patients with Suspected E-cigarette, or Vaping, Product Use-Associated Lung Injury - United States, November 2019.

CDC, the Food and Drug Administration (FDA), state and local health departments, and public health and clinical stakeholders are investigating a nationwide outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) (1). CDC has published recommendations for health care providers regarding EVALI (2-4). Recently, researchers from Utah and New York published proposed diagnosis and treatment algorithms for EVALI (5,6). EVALI remains a diagnosis of exclusion because, at present, no specific test or marker exists for its diagnosis, and evaluation should be guided by clinical judgment. Because patients with EVALI can experience symptoms similar to those associated with influenza or other respiratory infections (e.g., fever, cough, headache, myalgias, or fatigue), it might be difficult to differentiate EVALI from influenza or community-acquired pneumonia on initial assessment; EVALI might also co-occur with respiratory infections. This report summarizes recommendations for health care providers managing patients with suspected or known EVALI when respiratory infections such as influenza are more prevalent in the community than they have been in recent months (7). Recommendations include 1) asking patients with respiratory, gastrointestinal, or constitutional symptoms about the use of e-cigarette, or vaping, products; 2) evaluating those suspected to have EVALI with pulse oximetry and obtaining chest imaging, as clinically indicated; 3) considering outpatient management for clinically stable EVALI patients who meet certain criteria; 4) testing patients for influenza, particularly during influenza season, and administering antimicrobials, including antivirals, in accordance with established guidelines; 5) using caution when considering prescribing corticosteroids for outpatients, because this treatment modality has not been well studied among outpatients, and corticosteroids could worsen respiratory infections; 6) recommending evidence-based treatment strategies, including behavioral counseling, to help patients discontinue using e-cigarette, or vaping, products; and 7) emphasizing the importance of annual influenza vaccination for all persons aged ≥6 months, including patients who use e-cigarette, or vaping products.

Update: Characteristics of Patients in a National Outbreak of E-cigarette, or Vaping, Product Use-Associated Lung Injuries - United States, October 2019.

CDC, the Food and Drug Administration, state and local health departments, and other public health and clinical stakeholders are investigating a national outbreak of electronic-cigarette (e-cigarette), or vaping, product use-associated lung injury (EVALI) (1). As of October 22, 2019, 49 states, the District of Columbia (DC), and the U.S. Virgin Islands have reported 1,604 cases of EVALI to CDC, including 34 (2.1%) EVALI-associated deaths in 24 states. Based on data collected as of October 15, 2019, this report updates data on patient characteristics and substances used in e-cigarette, or vaping, products (2) and describes characteristics of EVALI-associated deaths. The median age of EVALI patients who survived was 23 years, and the median age of EVALI patients who died was 45 years. Among 867 (54%) EVALI patients with available data on use of specific e-cigarette, or vaping, products in the 3 months preceding symptom onset, 86% reported any use of tetrahydrocannabinol (THC)-containing products, 64% reported any use of nicotine-containing products, and 52% reported use of both. Exclusive use of THC-containing products was reported by 34% of patients and exclusive use of nicotine-containing products by 11%, and for 2% of patients, no use of either THC- or nicotine-containing products was reported. Among 19 EVALI patients who died and for whom substance use data were available, 84% reported any use of THC-containing products, including 63% who reported exclusive use of THC-containing products; 37% reported any use of nicotine-containing products, including 16% who reported exclusive use of nicotine-containing products. To date, no single compound or ingredient used in e-cigarette, or vaping, products has emerged as the cause of EVALI, and there might be more than one cause. Because most patients reported using THC-containing products before symptom onset, CDC recommends that persons should not use e-cigarette, or vaping, products that contain THC. In addition, because the specific compound or ingredient causing lung injury is not yet known, and while the investigation continues, persons should consider refraining from the use of all e-cigarette, or vaping, products.

Severe Pulmonary Disease Associated with Electronic-Cigarette-Product Use - Interim Guidance.

On September 6, 2019, this report was posted as an MMWR Early Release on the MMWR website (https://www.cdc.gov/mmwr). As of August 27, 2019, 215 possible cases of severe pulmonary disease associated with the use of electronic cigarette (e-cigarette) products (e.g., devices, liquids, refill pods, and cartridges) had been reported to CDC by 25 state health departments. E-cigarettes are devices that produce an aerosol by heating a liquid containing various chemicals, including nicotine, flavorings, and other additives (e.g., propellants, solvents, and oils). Users inhale the aerosol, including any additives, into their lungs. Aerosols produced by e-cigarettes can contain harmful or potentially harmful substances, including heavy metals such as lead, volatile organic compounds, ultrafine particles, cancer-causing chemicals, or other agents such as chemicals used for cleaning the device (1). E-cigarettes also can be used to deliver tetrahydrocannabinol (THC), the principal psychoactive component of cannabis, or other drugs; for example, "dabbing" involves superheating substances that contain high concentrations of THC and other plant compounds (e.g., cannabidiol) with the intent of inhaling the aerosol. E-cigarette users could potentially add other substances to the devices. This report summarizes available information and provides interim case definitions and guidance for reporting possible cases of severe pulmonary disease. The guidance in this report reflects data available as of September 6, 2019; guidance will be updated as additional information becomes available.

Good practices for the design, analysis, and interpretation of observational studies on birth spacing and perinatal health outcomes.

BACKGROUND: Meta-analyses of observational studies have shown that women with a shorter interpregnancy interval (the time from delivery to start of a subsequent pregnancy) are more likely to experience adverse pregnancy outcomes, such as preterm delivery or small for gestational age birth, than women who space their births further apart. However, the studies used to inform these estimates have methodological shortcomings. METHODS: In this commentary, we summarise the discussions of an expert workgroup describing good practices for the design, analysis, and interpretation of observational studies of interpregnancy interval and adverse perinatal health outcomes. RESULTS: We argue that inferences drawn from research in this field will be improved by careful attention to elements such as: (a) refining the research question to clarify whether the goal is to estimate a causal effect vs describe patterns of association; (b) using directed acyclic graphs to represent potential causal networks and guide the analytic plan of studies seeking to estimate causal effects; (c) assessing how miscarriages and pregnancy terminations may have influenced interpregnancy interval classifications; (d) specifying how key factors such as previous pregnancy loss, pregnancy intention, and maternal socio-economic position will be considered; and (e) examining if the association between interpregnancy interval and perinatal outcome differs by factors such as maternal age. CONCLUSION: This commentary outlines the discussions of this recent expert workgroup, and describes several suggested principles for study design and analysis that could mitigate many potential sources of bias.

Report of the Office of Population Affairs' expert work group meeting on short birth spacing and adverse pregnancy outcomes: Methodological quality of existing studies and future directions for research.

BACKGROUND: The World Health Organization (WHO) recommends that women wait at least 24 months after a livebirth before attempting a subsequent pregnancy to reduce the risk of adverse maternal, perinatal, and infant health outcomes. However, the applicability of the WHO recommendations for women in the United States is unclear, as breast feeding, nutrition, maternal age at first birth, and total fertility rate differs substantially between the United States and the low- and middle-resource countries upon which most of the evidence is based. METHODS: To inform guideline development for birth spacing specific to women in the United States, the Office of Population Affairs (OPA) convened an expert work group meeting in Washington, DC, on 14-15 September 2017 among reproductive, perinatal, paediatric, social, and public health epidemiologists; obstetrician-gynaecologists; biostatisticians; and experts in evidence synthesis related to women's health. RESULTS: Presentations and discussion topics included the methodological quality of existing studies, evaluation of the evidence for causal effects of short interpregnancy intervals on adverse perinatal and maternal health outcomes, good practices for future research, and identification of research gaps and priorities for future work. CONCLUSIONS: This report provides an overview of the presentations, discussions, and conclusions from the expert work group meeting.