During routine clinical practice, infectious disease physicians encounter patients with difficult-to-diagnose clinical syndromes and may order advanced molecular testing to detect pathogens. These tests may identify potential infectious causes for illness and allow clinicians to adapt treatments or stop unnecessary antimicrobials. Cases of pathogen-agnostic disease testing also provide an important window into known, emerging, and reemerging pathogens and may be leveraged as part of national sentinel surveillance. A survey of Emerging Infections Network members, a group of infectious disease providers in North America, was conducted in May 2023. The objective of the survey was to gain insight into how and when infectious disease physicians use advanced molecular testing for patients with difficult-to-diagnose infectious diseases, as well as to explore the usefulness of advanced molecular testing and barriers to use. Overall, 643 providers answered at least some of the survey questions; 478 (74%) of those who completed the survey had ordered advanced molecular testing in the last two years, and formed the basis for this study. Respondents indicated that they most often ordered broad-range 16S rRNA gene sequencing, followed by metagenomic next-generation sequencing and whole genome sequencing; and commented that in clinical practice, some, but not all tests were useful. Many physicians also noted several barriers to use, including a lack of national guidelines and cost, while others commented that whole genome sequencing had potential for use in outbreak surveillance. Improving frontline physician access, availability, affordability, and developing clear national guidelines for interpretation and use of advanced molecular testing could potentially support clinical practice and public health surveillance.

To better identify emerging or reemerging pathogens in patients with difficult-to-diagnose infections, it is important to improve access to advanced molecular testing methods. This is particularly relevant for cases where conventional microbiologic testing has been unable to detect the pathogen and the patient's specimens test negative. To assess the availability and utility of such testing for human clinical specimens, a literature review of published biomedical literature was conducted. From a corpus of more than 4,000 articles, a set of 34 reports was reviewed in detail for data on where the testing was being performed, types of clinical specimens tested, pathogen agnostic techniques and methods used, and results in terms of potential pathogens identified. This review assessed the frequency of advanced molecular testing, such as metagenomic next generation sequencing that has been applied to clinical specimens for supporting clinicians in caring for difficult-to-diagnose patients. Specimen types tested were from cerebrospinal fluid, respiratory secretions, and other body tissues and fluids. Publications included case reports and series, and there were several that involved clinical trials, surveillance studies, research programs, or outbreak situations. Testing identified both known human pathogens (sometimes in new sites) and previously unknown human pathogens. During this review, there were no apparent coordinated efforts identified to develop regional or national reports on emerging or reemerging pathogens. Therefore, development of a coordinated sentinel surveillance system that applies advanced molecular methods to clinical specimens which are negative by conventional microbiological diagnostic testing would provide a foundation for systematic characterization of emerging and underdiagnosed pathogens and contribute to national biodefense strategy goals.

The surveillance and identification of emerging, reemerging, and unknown infectious disease pathogens is essential to national public health preparedness and relies on fluidity, coordination, and interconnectivity between public and private pathogen surveillance systems and networks. Developing a national sentinel surveillance network with existing resources and infrastructure could increase efficiency, accelerate the identification of emerging public health threats, and support coordinated intervention strategies that reduce morbidity and mortality. However, implementing and sustaining programs to detect emerging and reemerging pathogens in humans using advanced molecular methods, such as metagenomic sequencing, requires making large investments in testing equipment and developing networks of clinicians, laboratory scientists, and bioinformaticians. In this study, we sought to gain an understanding of how federal government agencies currently support such pathogen agnostic testing of human specimens in the United States. We conducted a landscape analysis of federal agency websites for publicly accessible information on the availability and type of pathogen agnostic testing and details on flow of clinical specimens and data. The website analysis was supplemented by an expert review of results with representatives from the federal agencies. Operating divisions within the US Department of Health and Human Services and the US Department of Veterans Affairs have developed and sustained extensive clinical and research networks to obtain patient specimens and perform metagenomic sequencing. Metagenomic facilities supported by US agencies were not equally geographically distributed across the United States. Although many entities have work dedicated to metagenomics and/or support emerging infectious disease surveillance specimen collection, there was minimal formal collaboration across agencies.

To identify U.S. lead exposure risk hotspots, we expanded upon geospatial statistical methods from a published Michigan case study. The evaluation of identified hotspots using five lead indices, based on housing age and sociodemographic data, showed moderate-to-substantial agreement with state-identified higher-risk locations from nine public health department reports (45-78%) and with hotspots of children's blood lead data from Michigan and Ohio (e.g., Cohen's kappa scores of 0.49-0.63). Applying geospatial cluster analysis and 80th-100th percentile methods to the lead indices, the number of U.S. census tracts ranged from ∼8% (intersection of indices) to ∼41% (combination of indices). Analyses of the number of children <6 years old living in those census tracts revealed the states (e.g., Illinois, Michigan, New Jersey, New York, Ohio, Pennsylvania, Massachusetts, California, Texas) and counties with highest potential lead exposure risk. Results support use of available lead indices as surrogates to identify locations in the absence of consistent, complete blood lead level (BLL) data across the United States. Ground-truthing with local knowledge, additional BLL data, and environmental data is needed to improve identification and analysis of lead exposure and BLL hotspots for interventions. While the science evolves, these screening results can inform "deeper dive" analyses for targeting lead actions.

We draw artificial boundaries between our lives at work, at home, and in the community. Each person is living an integrated life where all of their environments (resources, physical environment, psychosocial environment, responsibilities/demands) interact to impact their safety, health, and well-being. Total Worker Health is an approach developed by the National Institute for Occupational Safety and Health (NIOSH) to address such interactions, and to advance science and practice for protecting workers' safety, health, and well-being. The Total Worker Health (TWH) approach represents an expansion of traditional occupational safety and health research and practice, with strong safety protections for workers as its foundation. The current paper provides an introduction to TWH, including: (1) Significance, (2) Historical Background, (3) Hierarchy of Controls, (4) Review of TWH Interventions, and (5) Future Opportunities. The reciprocal and interactive perspective of TWH is consistent with Skinnerian and other approaches to behavioral science, as well as organizational systems analysis approaches. With its behavioral and systems analysis roots, and associated historical emphasis on environmental conditions and interventions, the Organizational Behavior Management community can make great and important contributions in the TWH domain. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Exposure to certain chemicals prenatally and in childhood can impact development and may increase risk for attention-deficit/hyperactivity disorder (ADHD). Leveraging a larger set of literature searches conducted to synthesize results from longitudinal studies of potentially modifiable risk factors for childhood ADHD, we present meta-analytic results from 66 studies that examined the associations between early chemical exposures and later ADHD diagnosis or symptoms. Studies were eligible for inclusion if the chemical exposure occurred at least 6 months prior to measurement of ADHD diagnosis or symptomatology. Included papers were published between 1975 and 2019 on exposure to anesthetics (n = 5), cadmium (n = 3), hexachlorobenzene (n = 4), lead (n = 22), mercury (n = 12), organophosphates (n = 7), and polychlorinated biphenyls (n = 13). Analyses are presented for each chemical exposure by type of ADHD outcome reported (categorical vs. continuous), type of ADHD measurement (overall measures of ADHD, ADHD symptoms only, ADHD diagnosis only, inattention only, hyperactivity/impulsivity only), and timing of exposure (prenatal vs. childhood vs. cumulative), whenever at least 3 relevant effect sizes were available. Childhood lead exposure was positively associated with ADHD diagnosis and symptoms in all analyses except for the prenatal analyses (odds ratios (ORs) ranging from 1.60 to 2.62, correlation coefficients (CCs) ranging from 0.14 to 0.16). Other statistically significant associations were limited to organophosphates (CC = 0.11, 95% confidence interval (CI): 0.03-0.19 for continuous measures of ADHD outcomes overall), polychlorinated biphenyls (CC = 0.08, 95% CI: 0.02-0.14 for continuous measures of inattention as the outcome), and both prenatal and childhood mercury exposure (CC = 0.02, 95% CI: 0.00-0.04 for continuous measures of ADHD outcomes overall for either exposure window). Our findings provide further support for negative impacts of prenatal and/or childhood exposure to certain chemicals and raise the possibility that primary prevention and targeted screening could prevent or mitigate ADHD symptomatology. Furthermore, these findings support the need for regular review of regulations as our scientific understanding of the risks posed by these chemicals evolves.

PURPOSE: Although smoking cessation reduces the risk of all-cause mortality, evidence-based cessation treatments are underused. This study examined healthcare provider knowledge of evidence-based cessation treatments and associations between knowledge and clinical practice characteristics. DESIGN: Cross-sectional survey. SETTING: 2020 DocStyles. SUBJECTS: 1480 U.S. healthcare providers. MEASURES: Provider knowledge of availability of tobacco use disorder diagnostic criteria, clinical practice guideline availability, treatment efficacy, evidence-based counseling modalities, and medications approved by the U.S. Food and Drug Administration (FDA). ANALYSIS: Adjusted odds ratios (aORs), adjusted for personal and clinical practice characteristics. RESULTS: Less than half of respondents demonstrated high knowledge of availability of diagnostic criteria (36.8%), cessation treatment efficacy (33.2%), evidence-based counseling modalities (5.6%), and FDA-approved medications (40.1%). Significant differences were found between specialties: compared to internists, family physicians were less likely to have low knowledge of medications (aOR = .69, 95% CI = .53, .90) and obstetricians/gynecologists were more likely to have low knowledge of medications (aOR = 2.62, 95% CI = 1.82, 3.76). Overall, few associations between knowledge and clinical practice characteristics were identified. CONCLUSION: Most providers had low knowledge of the topics of interest, with little variation across clinical practice characteristics, indicating room for improvement. Efforts to improve provider knowledge of evidence-based treatments are an important component of a comprehensive approach to improving delivery and use of cessation interventions and increasing tobacco cessation.

Mucopolysaccharidosis type II (MPS-II, Hunter syndrome, OMIM:30990) is a lysosomal storage disorder (LSD) that results in iduronate 2-sulphatase (I2S) enzyme deficiency. MPS-II was added to the Recommended Uniform Screening Panel (RUSP) in August 2022; thus, there is an increased demand for multiplexing I2S into existing LSD screening assays. After incubation with LSD synthetic substrates, extracts are cleaned using liquid-liquid extraction with ethyl acetate or protein precipitation using acetonitrile (ACN). We investigated cold-induced water ACN phase separation (CIPS) to improve the combination of 6-plex and I2S extracts to create a 7-plex assay, and compared it to room temperature ACN and ethyl acetate liquid-liquid extraction. The extracts were dried and resuspended in the mobile phase, and then analyzed using an optimized 1.9 min injection-to-injection liquid chromatography method coupled with tandem mass spectrometry (LC-MS/MS). The combination of ACN and CIPS improved the detection for I2S products without significant detriment to other analytes, which is attributable to a more complete coagulation and separation of heme, proteins, and extracted residual salts. Using CIPS for sample cleanup in dried blood spots (DBS) appears to represent a promising and straightforward way of achieving cleaner sample extracts in a new 7-plex LSD screening panel.

INTRODUCTION: Although current cigarette smoking among US adults decreased from 42.4% in 1965 to 12.5% in 2020, prevalence is higher among certain racial and ethnic groups, including non-Hispanic American Indian and Alaska Native (AIAN) adults. METHODS: We examined trends in current cigarette smoking prevalence, population estimates, and relative disparity among US adults (aged ≥18 y) between 2011 and 2020 by using data from the National Health Interview Survey. SAS-callable SUDAAN was used to obtain prevalence and population estimates, and relative disparity was calculated on the basis of findings in the literature. Trends were significant at P < .05. RESULTS: From 2011 to 2020, linear decreases in prevalence and population estimates were observed for non-Hispanic White (20.6% to 13.3%; 32.1 million to 20.7 million), non-Hispanic Black (19.4% to 14.4%; 5.1 million to 4.0 million), and Hispanic (12.9% to 8.0%; 4.2 million to 3.3 million) adults. For non-Hispanic AIAN adults, prevalence remained around 27%, and a linear increase in the population estimate was observed from 400,000 to 510,000. Relative disparity did not change across racial and ethnic categories. CONCLUSION: Linear decreases have occurred between 2011 and 2020 for non-Hispanic White, non-Hispanic Black, and Hispanic adults who smoke, but the number of non-Hispanic AIAN adults who currently smoke has increased by 110,000, and relative disparities persist. To reduce racial and ethnic disparities in smoking, understanding how factors at multiple socioecologic levels impact smoking and helping to inform paths to equitable reach and implementation of tobacco control interventions for all population groups are needed.

BACKGROUND: Classical homocystinuria (HCU) results from deficient cystathionine β-synthase activity, causing elevated levels of Met and homocysteine (Hcy). Newborn screening (NBS) aims to identify HCU in pre-symptomatic newborns by assessing Met concentrations in first-tier screening. However, unlike Hcy, Met testing leads to a high number of false-positive and -negative results. Therefore, screening for Hcy directly in first-tier screening would be a better biomarker for use in NBS. METHODS: Dried blood spot (DBS) quality control and residual clinical specimens were used in analyses. Several reducing and maleimide reagents were investigated to aid in quantification of total Hcy (tHcy). The assay which was developed and validated was performed by flow injection analysis-tandem mass spectrometry (FIA-MS/MS). RESULTS: Interferents of tHcy measurement were identified, so selective derivatization of Hcy was employed. Using N-ethylmaleimide (NEM) to selectively derivatize Hcy allowed interferent-free quantification of tHcy by FIA-MS/MS in first-tier NBS. The combination of tris(2-carboxyethyl)phosphine (TCEP) and NEM yielded significantly less matrix effects compared to dithiothreitol (DTT) and NEM. Analysis of clinical specimens demonstrated that the method could distinguish between HCU-positive, presumptive normal newborns, and newborns receiving total parenteral nutrition. CONCLUSIONS: Here we present the first known validated method capable of screening tHcy in DBS during FIA-MS/S first-tier NBS.

For this state-of-science overview of geospatial approaches for identifying US communities with high lead-exposure risk, we compiled and summarized public data and national maps of lead indices and models, environmental lead indicators, and children's blood lead surveillance data. Currently available indices and models are primarily constructed from housing-age and sociodemographic data; differing methods, variables, data, weighting schemes, and geographic scales yield maps with different exposure risk profiles. Environmental lead indicators are available (e.g., air, drinking water, dust, soil) at different spatial scales, but key gaps remain. Blood lead level data have limitations as testing, reporting, and completeness vary across states. Mapping tools and approaches developed by federal agencies and other groups for different purposes present an opportunity for greater collaboration. Maps, data visualization tools, and analyses that synthesize available geospatial efforts can be evaluated and improved with local knowledge and blood lead data to refine identification of high-risk locations for prioritizing prevention efforts and targeting risk-reduction strategies. Remaining challenges are discussed along with a work-in-progress systematic approach for cross-agency data integration, toward advancing "whole-of-government" public health protection from lead exposures. (Am J Public Health. 2022;112(S7):S658-S669. https://doi.org/10.2105/AJPH.2022.307051).

Noncommunicable diseases (NCDs) are the leading cause of death in the world, and 80% of all NCD deaths occur in low- and middle-income countries (LMICs). The COVID-19 pandemic has demonstrated that patients with NCDs are at increased risk of becoming severely ill from the virus. Disproportionate investment in vertical health programs can result in health systems vulnerable to collapse when resources are strained, such as during pandemics. Although NCDs are largely preventable, globally there is underinvestment in efforts to address them. Integrating health systems to collectively address NCDs and infectious diseases through a wide range of services in a comprehensive manner reduces the economic burden of healthcare and strengthens the healthcare system. Health system resiliency is essential for health security. In this article, we provide an economically sound approach to incorporating NCDs into routine healthcare services in LMICs through improved alignment of institutions that support prevention and control of both NCDs and infectious diseases. Examples from Zambia's multisector interventions to develop and support a national NCD action plan can inform and encourage LMIC countries to invest in systems integration to reduce the social and economic burden of NCDs and infectious diseases.

The negative impact of lead exposure on young children and those who become pregnant is well documented but is not well known by those at highest risk from this hazard. Scientific evidence suggests that there is no known safe blood lead level (BLL), because even small amounts of lead can be harmful to a child's developing brain (1). In 2012, CDC introduced the population-based blood lead reference value (BLRV) to identify children exposed to more lead than most other children in the United States. The BLRV should be used as a guide to 1) help determine whether medical or environmental follow-up actions should be initiated for an individual child and 2) prioritize communities with the most need for primary prevention of exposure and evaluate the effectiveness of prevention efforts. The BLRV is based on the 97.5th percentile of the blood lead distribution in U.S. children aged 1-5 years from National Health and Nutrition Examination Survey (NHANES) data. NHANES is a complex, multistage survey designed to provide a nationally representative assessment of health and nutritional status of the noninstitutionalized civilian adult and child populations in the United States (2). The initial BLRV of 5 μg/dL, established in 2012, was based on data from the 2007-2008 and 2009-2010 NHANES cycles. Consistent with recommendations from a former advisory committee, this report updates CDC's BLRV in children to 3.5 μg/dL using NHANES data derived from the 2015-2016 and 2017-2018 cycles and provides helpful information to support adoption by state and local health departments, health care providers (HCPs), clinical laboratories, and others and serves as an opportunity to advance health equity and environmental justice related to preventable lead exposure. CDC recommends that public health and clinical professionals focus screening efforts on populations at high risk based on age of housing and sociodemographic risk factors. Public health and clinical professionals should collaborate to develop screening plans responsive to local conditions using local data. In the absence of such plans, universal BLL testing is recommended. In addition, jurisdictions should follow the Centers for Medicare & Medicaid Services requirement that all Medicaid-enrolled children be tested at ages 12 and 24 months or at age 24-72 months if they have not previously been screened (3).

BACKGROUND: Cigarette smoking is the leading cause of preventable disease and death in the United States. The tobacco product landscape has diversified to include electronic cigarettes (e-cigarettes). Adults with disabilities are more likely than adults without disabilities to smoke cigarettes, but within the current body of literature, there is limited information on the use of e-cigarettes among adults with disabilities. OBJECTIVE: To assess overall and state-specific prevalence of current e-cigarette use among adults by disability status, disability type, sex, and age. METHODS: Disability was defined as having serious difficulty with vision, hearing, mobility, cognition, or any difficulty with self-care or independent living. The Behavioral Risk Factor Surveillance System cross-sectional survey data (2016-2018; n = 1,150,775) were used to estimate state and District of Columbia prevalence of current e-cigarette use among adults (aged ≥18 years) with and without disabilities, overall and by disability type, sex, and age group. RESULTS: Median prevalence of current e-cigarette use was higher among adults with than without disabilities (6.5% vs. 4.3%, P < 0.05). Among adults with disabilities, use varied from 2.5% in DC to 10.0% in Colorado; median use was highest among those with cognitive disabilities (10.0%) and those aged 18-24 years (18.7%). CONCLUSIONS: Prevalence of current e-cigarette use was higher among adults with than without disabilities and varied across states by disability status, type, and age group. The findings underscore the need to monitor e-cigarette use among adults with disabilities and specifically include them in tobacco control policies and programs addressing e-cigarette use.

BACKGROUND: The assessment of real-world effectiveness of immunomodulatory medications for multisystem inflammatory syndrome in children (MIS-C) may guide therapy. METHODS: We analyzed surveillance data on inpatients younger than 21 years of age who had MIS-C and were admitted to 1 of 58 U.S. hospitals between March 15 and October 31, 2020. The effectiveness of initial immunomodulatory therapy (day 0, indicating the first day any such therapy for MIS-C was given) with intravenous immune globulin (IVIG) plus glucocorticoids, as compared with IVIG alone, was evaluated with propensity-score matching and inverse probability weighting, with adjustment for baseline MIS-C severity and demographic characteristics. The primary outcome was cardiovascular dysfunction (a composite of left ventricular dysfunction or shock resulting in the use of vasopressors) on or after day 2. Secondary outcomes included the components of the primary outcome, the receipt of adjunctive treatment (glucocorticoids in patients not already receiving glucocorticoids on day 0, a biologic, or a second dose of IVIG) on or after day 1, and persistent or recurrent fever on or after day 2. RESULTS: A total of 518 patients with MIS-C (median age, 8.7 years) received at least one immunomodulatory therapy; 75% had been previously healthy, and 9 died. In the propensity-score-matched analysis, initial treatment with IVIG plus glucocorticoids (103 patients) was associated with a lower risk of cardiovascular dysfunction on or after day 2 than IVIG alone (103 patients) (17% vs. 31%; risk ratio, 0.56; 95% confidence interval [CI], 0.34 to 0.94). The risks of the components of the composite outcome were also lower among those who received IVIG plus glucocorticoids: left ventricular dysfunction occurred in 8% and 17% of the patients, respectively (risk ratio, 0.46; 95% CI, 0.19 to 1.15), and shock resulting in vasopressor use in 13% and 24% (risk ratio, 0.54; 95% CI, 0.29 to 1.00). The use of adjunctive therapy was lower among patients who received IVIG plus glucocorticoids than among those who received IVIG alone (34% vs. 70%; risk ratio, 0.49; 95% CI, 0.36 to 0.65), but the risk of fever was unaffected (31% and 40%, respectively; risk ratio, 0.78; 95% CI, 0.53 to 1.13). The inverse-probability-weighted analysis confirmed the results of the propensity-score-matched analysis. CONCLUSIONS: Among children and adolescents with MIS-C, initial treatment with IVIG plus glucocorticoids was associated with a lower risk of new or persistent cardiovascular dysfunction than IVIG alone. (Funded by the Centers for Disease Control and Prevention.).

BACKGROUND: Nasopharyngeal specimens (NPS) are commonly used for SARS-CoV-2 testing but can be uncomfortable for patients. Self-collected saliva or anterior nasal specimens (ANS) for SARS-CoV-2 detection are less invasive but the sensitivity of these specimen types has not been thoroughly evaluated. METHODS: During September-November 2020, 730 adults undergoing SARS-CoV-2 testing at community testing events and homeless shelters in Denver provided self-collected saliva and ANS specimens before NPS collection and answered a short survey about symptoms and specimen preference. Specimens were tested for SARS-CoV-2 by rRT-PCR; viral culture was performed on a subset of specimens positive by rRT-PCR. Sensitivity of saliva and ANS for SARS-CoV-2 detection by rRT-PCR was measured against NPS. Subgroup analyses included test outcomes by symptom status and culture results. RESULTS: Sensitivity for SARS-CoV-2 detection by rRT-PCR appeared higher for saliva than for ANS (85% vs. 80%) and among symptomatic participants than among those without symptoms (94% vs. 29% for saliva; 87% vs. 50% for ANS). Among participants with culture-positive SARS-CoV-2 by any specimen type, sensitivity of saliva and ANS by rRT-PCR was 94% and 100%, respectively. Saliva and ANS were equally preferred by participants; most would undergo NPS again despite being least preferred. CONCLUSIONS: Saliva was slightly more sensitive than ANS for SARS-CoV-2 detection by rRT-PCR. Both saliva and ANS reliably detected SARS-CoV-2 among participants with symptoms. Self-collected saliva and ANS offer practical advantages, are preferred by patients, and might be most useful for testing people with COVID-19 symptoms.

Data on infants and toddlers (ITs) with von Willebrand disease (VWD) are lacking. We used data collected in the US Hemophilia Treatment Center Network (USHTCN) to describe birth characteristics, bleeding episodes, and complications experienced by 105 patients with VWD who were <2 years of age. In 68% of the patients, the reason for diagnostic testing was a family history of a bleeding disorder. The mean age at diagnosis was 7 months, with little variation by sex. Patients with type 2 VWD were diagnosed earlier than those with types 1 or 3 (P = .04), and those with a family history were diagnosed ∼4 months earlier than those with none (P < .001). Among the patients who experienced a bleeding event (70%), oral mucosa was the most common site of the initial bleeding episode (32%), followed by circumcision-related (12%) and intracranial/extracranial bleeding (10%). Forty-one percent of the initial bleeding events occurred before 6 months of age, and 68% of them occurred before the age of 1 year. Approximately 5% of the cohort experienced an intracranial hemorrhage; however, none was associated with delivery at birth. Bleeding patterns and rates were similar by sex (P = .40) and VWD type (P = .10). Forty-seven percent were treated with plasma-derived von Willebrand factor VIII concentrates. The results of this study indicate that a high percentage of ITs diagnosed with VWD and receiving care within the multidisciplinary structure of the USHTCN have a family history of VWD. In addition, bleeding events such as circumcision-related, oropharyngeal, and intracranial or extracranial episodes are common and are leading indicators for treatment.

BACKGROUND: Lead can adversely affect child health across a wide range of exposure levels. We describe the distribution of blood lead levels (BLLs) in U.S. children ages 1-11 y by selected sociodemographic and housing characteristics over a 40-y period. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) II (1976-1980), NHANES III (Phase 1: 1988-1991 and Phase II: 1991-1994), and Continuous NHANES (1999-2016) were used to describe the distribution of BLLs (in micrograms per deciliter; 1 μg/dL = 0.0483 μmol/L) in U.S. children ages 1-11 y from 1976 to 2016. For all children with valid BLLs (n = 27,122), geometric mean (GM) BLLs [95% confidence intervals (CI)] and estimated prevalence  ≥ 5 μg/dL (95% CI) were calculated overall and by selected characteristics, stratified by age group (1-5 y and 6-11 y). RESULTS: The GM BLL in U.S. children ages 1-5 y declined from 15.2 μg/dL (95% CI: 14.3, 16.1) in 1976-1980 to 0.83 μg/dL (95% CI: 0.78, 0.88) in 2011-2016, representing a 94.5% decrease over time. For children ages 6-11 y, GM BLL declined from 12.7 μg/dL (95% CI: 11.9, 13.4) in 1976-1980 to 0.60 μg/dL (95% CI: 0.58, 0.63) in 2011-2016, representing a 95.3% decrease over time. Even so, for the most recent period (2011-2016), estimates indicate that approximately 385,775 children ages 1-11 y had BLLs greater than or equal to the CDC blood lead reference value of 5 μg/dL. Higher GM BLLs were associated with non-Hispanic Black race/ethnicity, lower family income-to-poverty-ratio, and older housing age. DISCUSSION: Overall, BLLs in U.S. children ages 1-11 y have decreased substantially over the past 40 y. Despite these notable declines in population exposures to lead over time, higher GM BLLs are consistently associated with risk factors such as race/ethnicity, poverty, and housing age that can be used to target blood lead screening efforts. https://doi.org/10.1289/EHP7932.

IMPORTANCE: Coronavirus disease 2019 (COVID-19) affects the nervous system in adult patients. The spectrum of neurologic involvement in children and adolescents is unclear. OBJECTIVE: To understand the range and severity of neurologic involvement among children and adolescents associated with COVID-19. SETTING, DESIGN, AND PARTICIPANTS: Case series of patients (age <21 years) hospitalized between March 15, 2020, and December 15, 2020, with positive severe acute respiratory syndrome coronavirus 2 test result (reverse transcriptase-polymerase chain reaction and/or antibody) at 61 US hospitals in the Overcoming COVID-19 public health registry, including 616 (36%) meeting criteria for multisystem inflammatory syndrome in children. Patients with neurologic involvement had acute neurologic signs, symptoms, or diseases on presentation or during hospitalization. Life-threatening involvement was adjudicated by experts based on clinical and/or neuroradiologic features. EXPOSURES: Severe acute respiratory syndrome coronavirus 2. MAIN OUTCOMES AND MEASURES: Type and severity of neurologic involvement, laboratory and imaging data, and outcomes (death or survival with new neurologic deficits) at hospital discharge. RESULTS: Of 1695 patients (909 [54%] male; median [interquartile range] age, 9.1 [2.4-15.3] years), 365 (22%) from 52 sites had documented neurologic involvement. Patients with neurologic involvement were more likely to have underlying neurologic disorders (81 of 365 [22%]) compared with those without (113 of 1330 [8%]), but a similar number were previously healthy (195 [53%] vs 723 [54%]) and met criteria for multisystem inflammatory syndrome in children (126 [35%] vs 490 [37%]). Among those with neurologic involvement, 322 (88%) had transient symptoms and survived, and 43 (12%) developed life-threatening conditions clinically adjudicated to be associated with COVID-19, including severe encephalopathy (n = 15; 5 with splenial lesions), stroke (n = 12), central nervous system infection/demyelination (n = 8), Guillain-Barré syndrome/variants (n = 4), and acute fulminant cerebral edema (n = 4). Compared with those without life-threatening conditions (n = 322), those with life-threatening neurologic conditions had higher neutrophil-to-lymphocyte ratios (median, 12.2 vs 4.4) and higher reported frequency of D-dimer greater than 3 μg/mL fibrinogen equivalent units (21 [49%] vs 72 [22%]). Of 43 patients who developed COVID-19-related life-threatening neurologic involvement, 17 survivors (40%) had new neurologic deficits at hospital discharge, and 11 patients (26%) died. CONCLUSIONS AND RELEVANCE: In this study, many children and adolescents hospitalized for COVID-19 or multisystem inflammatory syndrome in children had neurologic involvement, mostly transient symptoms. A range of life-threatening and fatal neurologic conditions associated with COVID-19 infrequently occurred. Effects on long-term neurodevelopmental outcomes are unknown.

IMPORTANCE: Refinement of criteria for multisystem inflammatory syndrome in children (MIS-C) may inform efforts to improve health outcomes. OBJECTIVE: To compare clinical characteristics and outcomes of children and adolescents with MIS-C vs those with severe coronavirus disease 2019 (COVID-19). SETTING, DESIGN, AND PARTICIPANTS: Case series of 1116 patients aged younger than 21 years hospitalized between March 15 and October 31, 2020, at 66 US hospitals in 31 states. Final date of follow-up was January 5, 2021. Patients with MIS-C had fever, inflammation, multisystem involvement, and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase-polymerase chain reaction (RT-PCR) or antibody test results or recent exposure with no alternate diagnosis. Patients with COVID-19 had positive RT-PCR test results and severe organ system involvement. EXPOSURE: SARS-CoV-2. MAIN OUTCOMES AND MEASURES: Presenting symptoms, organ system complications, laboratory biomarkers, interventions, and clinical outcomes. Multivariable regression was used to compute adjusted risk ratios (aRRs) of factors associated with MIS-C vs COVID-19. RESULTS: Of 1116 patients (median age, 9.7 years; 45% female), 539 (48%) were diagnosed with MIS-C and 577 (52%) with COVID-19. Compared with patients with COVID-19, patients with MIS-C were more likely to be 6 to 12 years old (40.8% vs 19.4%; absolute risk difference [RD], 21.4% [95% CI, 16.1%-26.7%]; aRR, 1.51 [95% CI, 1.33-1.72] vs 0-5 years) and non-Hispanic Black (32.3% vs 21.5%; RD, 10.8% [95% CI, 5.6%-16.0%]; aRR, 1.43 [95% CI, 1.17-1.76] vs White). Compared with patients with COVID-19, patients with MIS-C were more likely to have cardiorespiratory involvement (56.0% vs 8.8%; RD, 47.2% [95% CI, 42.4%-52.0%]; aRR, 2.99 [95% CI, 2.55-3.50] vs respiratory involvement), cardiovascular without respiratory involvement (10.6% vs 2.9%; RD, 7.7% [95% CI, 4.7%-10.6%]; aRR, 2.49 [95% CI, 2.05-3.02] vs respiratory involvement), and mucocutaneous without cardiorespiratory involvement (7.1% vs 2.3%; RD, 4.8% [95% CI, 2.3%-7.3%]; aRR, 2.29 [95% CI, 1.84-2.85] vs respiratory involvement). Patients with MIS-C had higher neutrophil to lymphocyte ratio (median, 6.4 vs 2.7, P < .001), higher C-reactive protein level (median, 152 mg/L vs 33 mg/L; P < .001), and lower platelet count (<150 ×103 cells/μL [212/523 {41%} vs 84/486 {17%}, P < .001]). A total of 398 patients (73.8%) with MIS-C and 253 (43.8%) with COVID-19 were admitted to the intensive care unit, and 10 (1.9%) with MIS-C and 8 (1.4%) with COVID-19 died during hospitalization. Among patients with MIS-C with reduced left ventricular systolic function (172/503, 34.2%) and coronary artery aneurysm (57/424, 13.4%), an estimated 91.0% (95% CI, 86.0%-94.7%) and 79.1% (95% CI, 67.1%-89.1%), respectively, normalized within 30 days. CONCLUSIONS AND RELEVANCE: This case series of patients with MIS-C and with COVID-19 identified patterns of clinical presentation and organ system involvement. These patterns may help differentiate between MIS-C and COVID-19.

BACKGROUND: Older adults and people from certain racial and ethnic groups are disproportionately represented in coronavirus disease 2019 (COVID-19) hospitalizations and deaths. METHODS: Using data from the Premier Healthcare Database on 181( )813 hospitalized adults diagnosed with COVID-19 during March-September 2020, we applied multivariable log-binomial regression to assess the associations between age and race/ethnicity and COVID-19 clinical severity (intensive care unit [ICU] admission, invasive mechanical ventilation [IMV], and death) and to determine whether the impact of age on clinical severity differs by race/ethnicity. RESULTS: Overall, 84( )497 (47%) patients were admitted to the ICU, 29( )078 (16%) received IMV, and 27( )864 (15%) died in the hospital. Increased age was strongly associated with clinical severity when controlling for underlying medical conditions and other covariates; the strength of this association differed by race/ethnicity. Compared with non-Hispanic White patients, risk of death was lower among non-Hispanic Black patients (adjusted risk ratio, 0.96; 95% CI, 0.92-0.99) and higher among Hispanic/Latino patients (risk ratio [RR], 1.15; 95% CI, 1.09-1.20), non-Hispanic Asian patients (RR, 1.16; 95% CI, 1.09-1.23), and patients of other racial and ethnic groups (RR, 1.13; 95% CI, 1.06-1.21). Risk of ICU admission and risk of IMV were elevated among some racial and ethnic groups. CONCLUSIONS: These results indicate that age is a driver of poor outcomes among hospitalized persons with COVID-19. Additionally, clinical severity may be elevated among patients of some racial and ethnic minority groups. Public health strategies to reduce severe acute respiratory syndrome coronavirus 2 infection rates among older adults and racial and ethnic minorities are essential to reduce poor outcomes.

Residents and staff members of long-term care facilities (LTCFs), because they live and work in congregate settings, are at increased risk for infection with SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (1,2). In particular, skilled nursing facilities (SNFs), LTCFs that provide skilled nursing care and rehabilitation services for persons with complex medical needs, have been documented settings of COVID-19 outbreaks (3). In addition, residents of LTCFs might be at increased risk for severe outcomes because of their advanced age or the presence of underlying chronic medical conditions (4). As a result, the Advisory Committee on Immunization Practices has recommended that residents and staff members of LTCFs be offered vaccination in the initial COVID-19 vaccine allocation phase (Phase 1a) in the United States (5). In December 2020, CDC launched the Pharmacy Partnership for Long-Term Care Program* to facilitate on-site vaccination of residents and staff members at enrolled LTCFs. To evaluate early receipt of vaccine during the first month of the program, the number of eligible residents and staff members in enrolled SNFs was estimated using resident census data from the National Healthcare Safety Network (NHSN(†)) and staffing data from the Centers for Medicare & Medicaid Services (CMS) Payroll-Based Journal.(§) Among 11,460 SNFs with at least one vaccination clinic during the first month of the program (December 18, 2020-January 17, 2021), an estimated median of 77.8% of residents (interquartile range [IQR] = 61.3%- 93.1%) and a median of 37.5% (IQR = 23.2%- 56.8%) of staff members per facility received ≥1 dose of COVID-19 vaccine through the Pharmacy Partnership for Long-Term Care Program. The program achieved moderately high coverage among residents; however, continued development and implementation of focused communication and outreach strategies are needed to improve vaccination coverage among staff members in SNFs and other long-term care settings.

Exposure to lead, a toxic metal, can result in severe effects in children, including decreased ability to learn, permanent neurologic damage, organ failure, and death. CDC and other health care organizations recommend routine blood lead level (BLL) testing among children as part of well-child examinations to facilitate prompt identification of elevated BLL, eliminate source exposure, and provide medical and other services (1). To describe BLL testing trends among young children during the coronavirus disease 2019 (COVID-19) pandemic, CDC analyzed data reported from 34 state and local health departments about BLL testing among children aged <6 years conducted during January-May 2019 and January-May 2020. Compared with testing in 2019, testing during January-May 2020 decreased by 34%, with 480,172 fewer children tested. An estimated 9,603 children with elevated BLL were missed because of decreased BLL testing. Despite geographic variability, all health departments reported fewer children tested for BLL after the national COVID-19 emergency declaration (March-May 2020). In addition, health departments reported difficulty conducting medical follow-up and environmental investigations for children with elevated BLLs because of staffing shortages and constraints on home visits associated with the pandemic. Providers and public health agencies need to take action to ensure that children who missed their scheduled blood lead screening test, or who required follow-up on an earlier high BLL, be tested as soon as possible and receive appropriate care.

We describe coronavirus disease (COVID-19) among US food manufacturing and agriculture workers and provide updated information on meat and poultry processing workers. Among 742 food and agriculture workplaces in 30 states, 8,978 workers had confirmed COVID-19; 55 workers died. Racial and ethnic minority workers could be disproportionately affected by COVID-19.

OBJECTIVE: To assess the association between the change in statewide smoke-free laws and the rate of preterm or low birth weight delivery hospitalizations. DATA SOURCE: 2002-2013 Healthcare Cost and Utilization Project State Inpatient Databases. STUDY DESIGN: Quasi-experimental difference-in-differences design. We used multivariate logistic models to estimate the association between the change in state smoke-free laws and preterm or low birth weight delivery hospitalizations. The analyses were also stratified by maternal race/ethnicity to examine the differential effects by racial/ethnic groups. DATA COLLECTION/EXTRACTION METHODS: Delivery hospitalizations among women aged 15-49 years were extracted using the International Classification of Diseases, Ninth Revision, and Diagnosis-Related Group codes. PRINCIPAL FINDINGS: Non-Hispanic black mothers had a higher rate of preterm or low birth weight delivery hospitalization than other racial/ethnic groups. Overall, there was no association between the change in smoke-free laws and preterm or low birth weight delivery rate. Among non-Hispanic black mothers, the change in statewide smoke-free laws was associated with a 0.9-1.9 percentage point (P < .05) reduction in preterm or low birth weight delivery rate beginning in the third year after the laws took effect. There was no association among non-Hispanic white mothers. A decline in the black-white disparity of 0.6-1.6 percentage points (P < .05) in preterm or low birth weight delivery rates was associated with the change in state smoke-free laws. CONCLUSION: The change in state smoke-free laws was associated with a reduction in racial/ethnic disparities in preterm or low birth weight delivery hospitalizations in selected US states.

Hydroxychloroquine and chloroquine, primarily used to treat autoimmune diseases and to prevent and treat malaria, received national attention in early March 2020, as potential treatment and prophylaxis for coronavirus disease 2019 (COVID-19) (1). On March 20, the Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for chloroquine phosphate and hydroxychloroquine sulfate in the Strategic National Stockpile to be used by licensed health care providers to treat patients hospitalized with COVID-19 when the providers determine the potential benefit outweighs the potential risk to the patient.* Following reports of cardiac and other adverse events in patients receiving hydroxychloroquine for COVID-19 (2), on April 24, 2020, FDA issued a caution against its use(†) and on June 15, rescinded its EUA for hydroxychloroquine from the Strategic National Stockpile.(§) Following the FDA's issuance of caution and EUA rescindment, on May 12 and June 16, the federal COVID-19 Treatment Guidelines Panel issued recommendations against the use of hydroxychloroquine or chloroquine to treat COVID-19; the panel also noted that at that time no medication could be recommended for COVID-19 pre- or postexposure prophylaxis outside the setting of a clinical trial (3). However, public discussion concerning the effectiveness of these drugs on outcomes of COVID-19 (4,5), and clinical trials of hydroxychloroquine for prophylaxis of COVID-19 continue.(¶) In response to recent reports of notable increases in prescriptions for hydroxychloroquine or chloroquine (6), CDC analyzed outpatient retail pharmacy transaction data to identify potential differences in prescriptions dispensed by provider type during January-June 2020 compared with the same period in 2019. Before 2020, primary care providers and specialists who routinely prescribed hydroxychloroquine, such as rheumatologists and dermatologists, accounted for approximately 97% of new prescriptions. New prescriptions by specialists who did not typically prescribe these medications (defined as specialties accounting for ≤2% of new prescriptions before 2020) increased from 1,143 prescriptions in February 2020 to 75,569 in March 2020, an 80-fold increase from March 2019. Although dispensing trends are returning to prepandemic levels, continued adherence to current clinical guidelines for the indicated use of these medications will ensure their availability and benefit to patients for whom their use is indicated (3,4), because current data on treatment and pre- or postexposure prophylaxis for COVID-19 indicate that the potential benefits of these drugs do not appear to outweigh their risks.

Preventing coronavirus disease 2019 (COVID-19) in correctional and detention facilities* can be challenging because of population-dense housing, varied access to hygiene facilities and supplies, and limited space for isolation and quarantine (1). Incarcerated and detained populations have a high prevalence of chronic diseases, increasing their risk for severe COVID-19-associated illness and making early detection critical (2,3). Correctional and detention facilities are not closed systems; SARS-CoV-2, the virus that causes COVID-19, can be transmitted to and from the surrounding community through staff member and visitor movements as well as entry, transfer, and release of incarcerated and detained persons (1). To better understand SARS-CoV-2 prevalence in these settings, CDC requested data from 15 jurisdictions describing results of mass testing events among incarcerated and detained persons and cases identified through earlier symptom-based testing. Six jurisdictions reported SARS-CoV-2 prevalence of 0%-86.8% (median = 29.3%) from mass testing events in 16 adult facilities. Before mass testing, 15 of the 16 facilities had identified at least one COVID-19 case among incarcerated or detained persons using symptom-based testing, and mass testing increased the total number of known cases from 642 to 8,239. Case surveillance from symptom-based testing has likely underestimated SARS-CoV-2 prevalence in correctional and detention facilities. Broad-based testing can provide a more accurate assessment of prevalence and generate data to help control transmission (4).

Prolonged symptom duration and disability are common in adults hospitalized with severe coronavirus disease 2019 (COVID-19). Characterizing return to baseline health among outpatients with milder COVID-19 illness is important for understanding the full spectrum of COVID-19-associated illness and tailoring public health messaging, interventions, and policy. During April 15-June 25, 2020, telephone interviews were conducted with a random sample of adults aged ≥18 years who had a first positive reverse transcription-polymerase chain reaction (RT-PCR) test for SARS-CoV-2, the virus that causes COVID-19, at an outpatient visit at one of 14 U.S. academic health care systems in 13 states. Interviews were conducted 14-21 days after the test date. Respondents were asked about demographic characteristics, baseline chronic medical conditions, symptoms present at the time of testing, whether those symptoms had resolved by the interview date, and whether they had returned to their usual state of health at the time of interview. Among 292 respondents, 94% (274) reported experiencing one or more symptoms at the time of testing; 35% of these symptomatic respondents reported not having returned to their usual state of health by the date of the interview (median = 16 days from testing date), including 26% among those aged 18-34 years, 32% among those aged 35-49 years, and 47% among those aged ≥50 years. Among respondents reporting cough, fatigue, or shortness of breath at the time of testing, 43%, 35%, and 29%, respectively, continued to experience these symptoms at the time of the interview. These findings indicate that COVID-19 can result in prolonged illness even among persons with milder outpatient illness, including young adults. Effective public health messaging targeting these groups is warranted. Preventative measures, including social distancing, frequent handwashing, and the consistent and correct use of face coverings in public, should be strongly encouraged to slow the spread of SARS-CoV-2.

Meat and poultry processing facilities face distinctive challenges in the control of infectious diseases, including coronavirus disease 2019 (COVID-19) (1). COVID-19 outbreaks among meat and poultry processing facility workers can rapidly affect large numbers of persons. Assessment of COVID-19 cases among workers in 115 meat and poultry processing facilities through April 27, 2020, documented 4,913 cases and 20 deaths reported by 19 states (1). This report provides updated aggregate data from states regarding the number of meat and poultry processing facilities affected by COVID-19, the number and demographic characteristics of affected workers, and the number of COVID-19-associated deaths among workers, as well as descriptions of interventions and prevention efforts at these facilities. Aggregate data on confirmed COVID-19 cases and deaths among workers identified and reported through May 31, 2020, were obtained from 239 affected facilities (those with a laboratory-confirmed COVID-19 case in one or more workers) in 23 states.* COVID-19 was confirmed in 16,233 workers, including 86 COVID-19-related deaths. Among 14 states reporting the total number of workers in affected meat and poultry processing facilities (112,616), COVID-19 was diagnosed in 9.1% of workers. Among 9,919 (61%) cases in 21 states with reported race/ethnicity, 87% occurred among racial and ethnic minority workers. Commonly reported interventions and prevention efforts at facilities included implementing worker temperature or symptom screening and COVID-19 education, mandating face coverings, adding hand hygiene stations, and adding physical barriers between workers. Targeted workplace interventions and prevention efforts that are appropriately tailored to the groups most affected by COVID-19 are critical to reducing both COVID-19-associated occupational risk and health disparities among vulnerable populations. Implementation of these interventions and prevention efforts(dagger) across meat and poultry processing facilities nationally could help protect workers in this critical infrastructure industry.

Descriptions of coronavirus disease 2019 (COVID-19) in the United States have focused primarily on hospitalized patients. Reports documenting exposures to SARS-CoV-2, the virus that causes COVID-19, have generally been described within congregate settings, such as meat and poultry processing plants (1) and long-term care facilities (2). Understanding individual behaviors and demographic characteristics of patients with COVID-19 and risks for severe illness requiring hospitalization can inform efforts to reduce transmission. During April 15-May 24, 2020, telephone interviews were conducted with a random sample of adults aged >/=18 years who had positive reverse transcription-polymerase chain reaction (RT-PCR) test results for SARS-CoV-2 in outpatient and inpatient settings at 11 U.S. academic medical centers in nine states. Respondents were contacted 14-21 days after SARS-CoV-2 testing and asked about their demographic characteristics, underlying chronic conditions, symptoms experienced on the date of testing, and potential exposures to SARS-CoV-2 during the 2 weeks before illness onset (or the date of testing among those who did not report symptoms at the time of testing). Among 350 interviewed patients (271 [77%] outpatients and 79 [23%] inpatients), inpatients were older, more likely to be Hispanic and to report dyspnea than outpatients. Fewer inpatients (39%, 20 of 51) reported a return to baseline level of health at 14-21 days than did outpatients (64%, 150 of 233) (p = 0.001). Overall, approximately one half (46%) of patients reported known close contact with someone with COVID-19 during the preceding 2 weeks. This was most commonly a family member (45%) or a work colleague (34%). Approximately two thirds (64%, 212 of 333) of participants were employed; only 35 of 209 (17%) were able to telework. These findings highlight the need for screening, case investigation, contact tracing, and isolation of infected persons to control transmission of SARS-CoV-2 infection during periods of community transmission. The need for enhanced measures to ensure workplace safety, including ensuring social distancing and more widespread use of cloth face coverings, are warranted (3).