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Background: Short-term fine particulate matter (PM2.5) exposure is positively associated with acute cardiovascular and respiratory events. Understanding whether this association varies across specific cardiovascular and respiratory conditions has important biologic, clinical, and public health implications.Methods: We conducted a time-stratified case-crossover study of hospitalizations from 2000 through 2014 among United States Medicare beneficiaries aged 65+. The outcomes were hospitalizations with any of 57 cardiovascular and 32 respiratory discharge diagnoses. We estimated associations with two-day moving average PM2.5 as a piecewise linear term with a knot at PM2.5 = 25 g/m3. We used Multi-Outcome Regression with Tree-structured Shrinkage (MOReTreeS) to identify de novo groups of related diseases such that PM2.5 associations are: (1) similar within outcome groups; but (2) different between outcome groups. We adjusted for temperature, humidity, and individual-level characteristics. We introduce an R package, moretrees.Results: Our dataset included 16,007,293 cardiovascular and 8,690,837 respiratory hospitalizations. Of 57 cardiovascular diseases, 51 were grouped and positively associated with PM2.5. We observed a stronger positive association for heart failure, which formed a separate group. We observed negative associations for groups containing the outcomes other aneurysm and intracranial hemorrhage. Of 32 respiratory outcomes, 31 were grouped and were positively associated with PM2.5. Influenza formed a separate group with a negative association.Conclusions: We used a new statistical approach, MOReTreeS, to uncover variation in the association between short-term PM2.5 exposure and hospitalizations for cardiovascular and respiratory causes controlling for patient characteristics, time trends, and environmental confounders. [ABSTRACT FROM AUTHOR]

Background: More intense tropical cyclones (TCs) are expected in the future under a warming climate scenario, but little is known about their mortality effect pattern across countries and over decades. We aim to evaluate the TC-specific mortality risks, periods of concern (POC) and characterize the spatiotemporal pattern and exposure-response (ER) relationships on a multicountry scale., Methods and Findings: Daily all-cause, cardiovascular, and respiratory mortality among the general population were collected from 494 locations in 18 countries or territories during 1980 to 2019. Daily TC exposures were defined when the maximum sustained windspeed associated with a TC was ≥34 knots using a parametric wind field model at a 0.5° × 0.5° resolution. We first estimated the TC-specific mortality risks and POC using an advanced flexible statistical framework of mixed Poisson model, accounting for the population changes, natural variation, seasonal and day of the week effects. Then, a mixed meta-regression model was used to pool the TC-specific mortality risks to estimate the overall and country-specific ER relationships of TC characteristics (windspeed, rainfall, and year) with mortality. Overall, 47.7 million all-cause, 15.5 million cardiovascular, and 4.9 million respiratory deaths and 382 TCs were included in our analyses. An overall average POC of around 20 days was observed for TC-related all-cause and cardiopulmonary mortality, with relatively longer POC for the United States of America, Brazil, and Taiwan (>30 days). The TC-specific relative risks (RR) varied substantially, ranging from 1.04 to 1.42, 1.07 to 1.77, and 1.12 to 1.92 among the top 100 TCs with highest RRs for all-cause, cardiovascular, and respiratory mortality, respectively. At country level, relatively higher TC-related mortality risks were observed in Guatemala, Brazil, and New Zealand for all-cause, cardiovascular, and respiratory mortality, respectively. We found an overall monotonically increasing and approximately linear ER curve of TC-related maximum sustained windspeed and cumulative rainfall with mortality, with heterogeneous patterns across countries and regions. The TC-related mortality risks were generally decreasing from 1980 to 2019, especially for the Philippines, Taiwan, and the USA, whereas potentially increasing trends in TC-related all-cause and cardiovascular mortality risks were observed for Japan., Conclusions: The TC mortality risks and POC varied greatly across TC events, locations, and countries. To minimize the TC-related health burdens, targeted strategies are particularly needed for different countries and regions, integrating epidemiological evidence on region-specific POC and ER curves that consider across-TC variability., Competing Interests: YG is a member of the Editorial Board of PLOS Medicine. All other authors declare no competing interests., (Copyright: © 2024 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Abstract To communicate health risks associated with short-term changes in air pollution, the US EPA reports local air quality through the Air Quality Index (AQI). However, it remains unclear whether the current regulatory-based, single-pollutant AQI fully represents the actual risks of air pollution-related illness. A revised index using a multi-pollutant approach based on health effects could potentially improve public health by better reflecting the health risks associated with exposure to multiple pollutants. Using time-series analysis, daily AQI values of four criteria pollutants (NO 2 , O 3 , PM 2.5 , and SO 2) in Bronx and Queens Counties of New York from 2005 to 2010 were regressed against total respiratory emergency department (ED) visits using a Poisson generalized linear model to generate region-specific coefficients (NO 2 : 0.011; O 3 : 0.0027; PM 2.5 : 0.0022; SO 2 : 0.0013), which were used to develop a multi-pollutant health-based air quality index. Multi-pollutant index models and single-pollutant EPA AQI values were regressed against total respiratory ED visits from 2011 to 2013 to determine the association of index values with population-level health outcomes. Based on time-series analysis, each pollutant considered was shown to have significant positive associations with respiratory ED visits for at least part of the year and was therefore eligible for potential inclusion in a multi-pollutant index. A log-transformed, multi-pollutant health-based model with NO 2 , O 3 , PM 2.5 , and SO 2 was found to have more consistent associations throughout the high-O 3 (April–September) (1.03, 95% CI [1.01–1.05]) and low- O 3 (October–March) (1.03, 95% CI [1.01–1.05]) seasons with total respiratory ED visits as compared to AQI values. Associations between respiratory ED visits and the AQI were not significant during the high-O 3 season (high-O 3 : 1.00, 95% CI [0.99–1.02]. These results indicate that a single-pollutant index may at times inadequately communicate the full adverse health risks of air pollution. A multi-pollutant index, that was adjusted to ensure a relatively normal distribution of index values, was able to reflect population level health outcomes during the high-O 3 season when air pollution mixtures become more complex, while the currently utilized AQI could not represent population-level air pollution health risks during the high-O 3 season. The development and validation of a multi-pollutant index for use in the US is something that may merit consideration in future updates to air quality standards under the Clean Air Act. Local jurisdictions may wish to act sooner to improve risk communication of outdoor air pollution. Highlights • Positive association for respiratory morbidity and multiple air pollutants in NYC. • EPA AQI not associated with respiratory outcomes during high-O 3 season. • Health-based AQI predictive of respiratory risks during high- and low-O 3 seasons. • Adjustments to create index values with a normal distribution improved results. [ABSTRACT FROM AUTHOR]

Background: The arm circumference is a feasible and reliable indicator in evaluating the nutritional status of children. However, its application in general adults has yet to be thoroughly investigated., Objective: This study aimed to evaluate the association between mid-upper arm circumferences (MUACs) and mortality in general adults., Methods: The nationally representative cohort from the National Health and Nutrition Examination Survey (1999-2018) was analyzed with mortality information obtained through linkage to the National Death Index. The baseline MUACs were collected as exposure. Survey-weighted Cox proportional hazard regressions were performed to estimate the hazard ratios (HRs) and 95% confidential intervals (CIs) of mortality risk for individuals with different MUACs. Restricted cubic spline analyses were performed to examine the nonlinear association of MUAC with all-cause and cause-specific mortality., Results: A total of 52,159 participants were included in this study. During a median follow-up time of 117 months, 7157 deaths were documented, with leading causes of cardiovascular disease (CVD), cancer, and respiratory disease. Individuals in the first quartile (Q1) of MUAC tended to have higher all-cause mortality risk than the rest after full adjustment. Similarly, CVD mortality risk in Q1 was higher than that in the second quartile (Q2) and the third quartile (Q3); respiratory mortality risk in Q1 was higher than in Q2. MUAC was non-linearly associated with all-cause mortality and CVD mortality. Individuals in Q1 MUAC (≤ 29.3) tended to have higher all-cause mortality risk, with HRs (95% CIs) estimated to be 0.76 (0.67-0.87) for Q2 (29.4, 32.5), 0.69 (0.59-0.81) for Q3 (32.6, 36.0), and 0.59 (0.46-0.75) for Q4 (≥ 36.1) after adjustment of demographic, lifestyle, and comorbidity covariates. Similarly, compared with Q1, HRs (95% CIs) for CVD mortality were estimated to be 0.73 (0.58-0.93) for Q2 and 0.57 (0.43-0.47) for Q3; HRs (95% CIs) for respiratory mortality was estimated to be 0.57 (95% CI, 0.37-0.87) for Q2 with other differences not significant., Conclusion: The MUAC was inversely associated with long-term mortality in general adults in the United States and may serve as a valuable measurement in adult health evaluations., (© 2023. The Author(s).)

Respiratory syncytial virus (RSV) is a cause of severe respiratory illness in older adults. In May 2023, the Food and Drug Administration approved the first vaccines for prevention of RSV-associated lower respiratory tract disease in adults aged ≥60 years. Since May 2022, the Advisory Committee on Immunization Practices (ACIP) Respiratory Syncytial Virus Vaccines Adult Work Group met at least monthly to review available evidence regarding the safety, immunogenicity, and efficacy of these vaccines among adults aged ≥60 years. On June 21, 2023, ACIP voted to recommend that adults aged ≥60 years may receive a single dose of an RSV vaccine, using shared clinical decision-making. This report summarizes the body of evidence considered for this recommendation and provides clinical guidance for the use of RSV vaccines in adults aged ≥60 years. RSV vaccines have demonstrated moderate to high efficacy in preventing RSV-associated lower respiratory tract disease and have the potential to prevent substantial morbidity and mortality among older adults; postmarketing surveillance will direct future guidance., (Copyright © 2023. Published by Elsevier Inc.)

Objective. To survey the literature regarding climate-sensitive diseases (CSD) and the impacts of climate changes on health. Method. This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The Lilacs, SciELO, Scopus, and PubMed databases were searched in July 2017 without temporal restrictions for articles published in in Portuguese, English and Spanish. The following search strategy was used in all databases: (climate) AND (disease) AND (sensitive). Results. The systematic review included 106 articles, most of which focused on dengue, malaria, and respiratory and cardiovascular diseases. The most commonly studied climate variables were temperature and precipitation. The studies revealed a relationship between the incidence of certain diseases, especially cardiovascular and respiratory diseases, dengue, malaria, and arboviral diseases, and climate conditions in different regions of the world. This relationship was analyzed considering both past data on the incidence of diseases and climate variables and projections regarding the future incidence of diseases according to expected climate variations. A greater number of studies was performed by authors originating from developed countries. The world regions most often studied were China, the United States, Australia, and Brazil. Conclusions. Despite the increase in the number of published articles on this theme, a greater number of climate and environmental variables must be studied, with expansion of studies to additional regions in the world. [ABSTRACT FROM AUTHOR]

Climate change has brought increasing attention to the assessment of health risks associated with climate and extreme events. Drought is a complex climate phenomenon that has been increasing in frequency and severity both locally and globally due to climate change. However, the health risks of drought are often overlooked, especially in places such as the United States, as the pathways to health impacts are complex and indirect. This study aims to conduct a comprehensive assessment of the effects of monthly drought exposure on respiratory mortality for NOAA climate regions in the United States from 2000 to 2018. A two-stage model was applied to estimate the location-specific and overall effects of respiratory risk associated with two different drought indices over two timescales (the US Drought Monitor and the 6-month and 12-month Evaporative Demand Drought Index). During moderate and severe drought exposure, respiratory mortality risk ratio in the general population increased up to 6.0% (95% Cr: 4.8 to 7.2) in the Northeast, 9.0% (95% Cr: 4.9 to 13.3) in the Northern Rockies and Plains, 5.2% (95% Cr: 3.9 to 6.5) in the Ohio Valley, 3.5% (95% Cr: 1.9 to 5.0) in the Southeast, and 15.9% (95% Cr: 10.8 to 20.4) in the Upper Midwest. Our results showed that age, ethnicity, sex (both male and female), and urbanicity (both metro and non-metro) resulted in more affected population subgroups in certain climate regions. The magnitude and direction of respiratory risk ratio differed across NOAA climate regions. These results demonstrate a need for policymakers and communities to develop more effective strategies to mitigate the effects of drought across regions.

People with respiratory disease have increased risk of developing frailty, which is associated with worse health outcomes. There is growing evidence of the role of rehabilitation in managing frailty in people with respiratory disease. However, several challenges remain regarding optimal methods of identifying frailty and delivering rehabilitation for this population. The aims of this American Thoracic Society workshop were to outline key definitions and concepts around rehabilitation for people with respiratory disease and frailty, synthesize available evidence, and explore how programs may be adapted to align to the needs and experiences of this population. Across two half-day virtual workshops, 20 professionals from diverse disciplines, professions, and countries discussed key developments and identified opportunities for future research, with additional input via online correspondence. Participants highlighted a "frailty rehabilitation paradox" whereby pulmonary rehabilitation can effectively reduce frailty, but programs are challenging for some individuals with frailty to complete. Frailty should not limit access to rehabilitation; instead, the identification of frailty should prompt comprehensive assessment and tailored support, including onward referral for additional specialist input. Exercise prescriptions that explicitly consider symptom burden and comorbidities, integration of additional geriatric or palliative care expertise, and/or preemptive planning for disruptions to participation may support engagement and outcomes. To identify and measure frailty in people with respiratory disease, tools should be selected on the basis of sensitivity, specificity, responsiveness, and feasibility for their intended purpose. Research is required to expand understanding beyond the physical dimensions of frailty and to explore the merits and limitations of telerehabilitation or home-based pulmonary rehabilitation for people with chronic respiratory disease and frailty.

Background: Home hospital (HH) care is hospital-level substitutive care delivered at home for acutely ill patients who traditionally would be cared for in the hospital. Despite HH care programs operating successfully for years and scientific evidence of similar or better outcomes compared with bricks-and-mortar care, HH care outcomes in the United States for respiratory disease have not been evaluated., Research Question: Do outcomes differ between patients admitted to HH care with acute respiratory illness vs those with other acute general medical conditions?, Study Design and Methods: This was a retrospective evaluation of prospectively collected data of patients admitted to HH care (2017-2021). We compared patients requiring admission with respiratory disease (asthma exacerbation [26%], acute exacerbation of COPD [33%], and non-COVID-19 pneumonia [41%]) to all other patients admitted to HH care. During HH care, patients received two nurse and one physician visit daily, IV medications, advanced respiratory therapies, and continuous heart and respiratory rate monitoring. Main outcomes were acute and postacute health care use and safety., Results: We analyzed 1,031 patients; 24% were admitted for respiratory disease. Patients with and without respiratory disease were similar: mean age, 68 ± 17 years, 62% women, and 48% White. Patients with respiratory disease more often were active smokers (21% vs 9%; P < .001). Eighty percent of patients showed an FEV 1 to FVC ratio of ≤ 70; 28% showed a severe or very severe obstructive pattern (n = 118). During HH care, patients with respiratory disease showed less health care use: length of stay (mean, 3.4 vs 4.6 days), laboratory orders (median, 0 vs 2), IV medication (43% vs 73%), and specialist consultation (2% vs 7%; P < .001 for all). Ninety-six percent of patients completed the full admission at home with no mortality in the respiratory group. Within 30 days of discharge, both groups showed similar readmission, ED presentation, and mortality rates., Interpretation: HH care is as safe and effective for patients with acute respiratory disease as for those with other acute general medical conditions. If scaled, it can generate significant high-value capacity for health systems and communities, with opportunities to advance the complexity of care delivered., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: During 2008-15, the Marcellus shale region of the US state of Pennsylvania experienced a boom in unconventional natural gas development (UNGD) or "fracking". However, despite much public debate, little is known about the effects of UNGD on population health in local communities. Among other mechanisms, air pollution from UNGD might affect individuals living nearby through cardiovascular or respiratory disease, and older adults could be particularly susceptible., Methods: To study the health impacts of Pennsylvania's fracking boom, we exploited the ban on UNGD in neighbouring New York state. Using 2002-15 Medicare claims, we conducted difference-in-differences analyses over multiple timepoints to estimate the risk of living near UNGD for hospitalisation with acute myocardial infarction (AMI), chronic obstructive pulmonary disease (COPD) and bronchiectasis, heart failure, ischaemic heart disease, and stroke among older adults (aged ≥65 years)., Findings: Pennsylvania ZIP codes that started UNGD in 2008-10 were associated with more hospitalisations for cardiovascular diseases in 2012-15 than would be expected in the absence of UNGD. Specifically, in 2015, we estimated an additional 11·8, 21·6, and 20·4 hospitalisations for AMI, heart failure, and ischaemic heart disease, respectively, per 1000 Medicare beneficiaries. Hospitalisations increased even as UNGD growth slowed. Results were robust in sensitivity analyses., Interpretation: Older adults living near UNGD could be at high risk of poor cardiovascular outcomes. Mitigation policies for existing UNGD might be needed to address current and future health risks. Future consideration of UNGD should prioritise local population health., Funding: University of Chicago and Argonne National Laboratories., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Potential conflicts of interest. E. A. F. S. reports the following: grants and consulting fees to the institution from Merck & Co. and Pfizer Inc; grants to the institution from Astra Zeneca Inc., Roche Pharmaceuticals, and Johnson and Johnson; consulting fees to the institution from Sanofi, Cidara Therapeutics, Adiago Therapeutics Inc, and Nuance Pharmaceuticals; manuscript writing support from Sanofi and Astra Zeneca Inc.; support for attending a meeting at Astra Zeneca Inc. and participation on a Data and Safety Monitoring Board from Abbvie Inc., GlaxoSmithKline plc, and the Bill & Melinda Gates Foundation, all outside the submitted work. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Context Ozone has been associated with various adverse health effects, including increased rates of hospital admissions and exacerbation of respiratory illnesses. Although numerous time-series studies have estimated associations between day-to-day variation in ozone levels and mortality counts, results have been inconclusive. Objective To investigate whether short-term (daily and weekly) exposure to ambient ozone is associated with mortality in the United States. Design and Setting Using analytical methods and databases developed for the National Morbidity, Mortality, and Air Pollution Study, we estimated a national average relative rate of mortality associated with short-term exposure to ambient ozone for 95 large US urban communities from 1987-2000. We used distributed-lag models for estimating community-specific relative rates of mortality adjusted for time-varying confounders (particulate matter, weather, seasonality, and long-term trends) and hierarchical models for combining relative rates across communities to estimate a national average relative rate, taking into account spatial heterogeneity. Main Outcome Measure Daily counts of total non–injury-related mortality and cardiovascular and respiratory mortality in 95 large US communities during a 14-year period. Results A 10-ppb increase in the previous week’s ozone was associated with a 0.52% increase in daily mortality (95% posterior interval [PI], 0.27%-0.77%) and a 0.64% increase in cardiovascular and respiratory mortality (95% PI, 0.31%-0.98%). Effect estimates for aggregate ozone during the previous week were larger than for models considering only a single day’s exposure. Results were robust to adjustment for particulate matter, weather, seasonality, and long-term trends. Conclusions These results indicate a statistically significant association between short-term changes in ozone and mortality on average for 95 large US urban communities, which include about 40% of the total US p... [ABSTRACT FROM AUTHOR]

Early in the COVID-19 pandemic, demand for N95 respirators far exceeded the supply, leading to widespread shortages. Initially, the US Centers for Disease Control and Prevention did not recommend N95 respirators in nonhealthcare settings, in order to reserve them for healthcare workers. As N95s became more available, the recommendations were updated in May 2021 to include N95 respirators for nonhealthcare settings. In this study, we estimated the numbers of N95s needed for nonhealthcare essential workers in the United States. This information is valuable for crisis preparedness and planning for future large-scale communicable respiratory infectious disease epidemics or pandemics. We adapted a spreadsheet-based tool originally built to estimate the potential demand for N95 respirators during an influenza pandemic. We defined nonhealthcare essential occupations according to the 2020 US Department of Homeland Security guidance and used US Bureau of Labor Statistics employment numbers and Occupational Information Network data as model parameters. We modeled minimum, intermediate, and maximum N95 provision scenarios (as 1, 2, and 5 N95 respirators, respectively) per week per worker, for pandemic durations of 15 and 40 weeks. For 85.15 million nonhealthcare essential workers during a 15-week pandemic, an estimated 1.3 billion N95 respirators would be needed under minimum provision scenarios, 2.6 billion for intermediate provision, and 6.4 billion for maximum provision. During a 40-week pandemic, these estimates increased to 3.4 billion, 6.8 billion, and 17 billion. Public health authorities and policymakers can use these estimates when considering workplace respirator-wearing practices, including prioritization of allocation, for nonhealthcare essential workers. Our novel spreadsheet-based tool can also be used to quickly generate estimates of other preparedness and response equipment.

Our objective was to describe community-acquired pneumonia (CAP) among patients ≥85 years and compare them to patients aged 65-74. This was a retrospective cohort study. The study setting included 638 hospitals in the USA participating in the Premier database from 2010 to 2015. The study participants were 488,382 adults aged ≥65 years hospitalized with CAP. Patients ≥85 years were more likely to be white (79.8% vs 76.2%), female (58.1% vs 48.3%), and admitted with aspiration pneumonia (17.1% vs 7.0%) as compared with those aged 65-75 years. They had higher rates of dementia (30.4% vs 7.8%), but lower rates of diabetes (11.2% vs 17.6%) and chronic obstructive pulmonary disease (25.5% vs 54.7%). While Staphylococcus aureus (33.4%) was the most common pathogen across all age groups, patients aged ≥85 were more likely to have Escherichia coli pneumonia (16.1% vs 10.7%) compared with those aged 65-74. In adjusted models, patients aged ≥85 had greater in-hospital mortality (OR 1.14, 95% CI 1.11 to 1.18), but were less likely to be admitted to the intensive care unit (OR 0.54, 95% CI 0.53 to 0.55) and receive mechanical ventilation (OR 0.47, 95% CI 0.46 to 0.48). They also had lower rates of acute kidney injury (OR 0.95, 95% CI 0.91 to 1.00) and Clostridium difficile infection (OR 0.91, 95% CI 0.85 to 0.99), shorter lengths of stay (mean multiplier 0.93, 95% CI 0.92 to 0.93) and lower cost (mean multiplier 0.81, 95% CI 0.80 to 0.81), and were more likely to be discharged to a skilled nursing facility (OR 2.19, 95% CI 2.15 to 2.24) or hospice (OR 2.19, 95% CI 2.11 to 2.27). In conclusion, patients aged ≥85 have different comorbidities and etiologies of CAP, receive less intense treatment, and have greater mortality than patients between 65 and 75 years., Competing Interests: Competing interests: P-CY, AD, and MBR were supported by funds from the Agency for Healthcare Research and Quality (R01HS024277)., (© American Federation for Medical Research 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

The adverse influences of climate change are manifesting as health burdens relevant to clinical practice, affecting the very underpinnings of health and stressing the health care system. Emergency medicine is likely to bear a large burden, with its focus on urgent and emergency care, through its role as a safety-net provider for vulnerable populations and as a leader in disaster medicine. Clinically, climate change is affecting emergency medicine practice through the amplification of climate-related disease patterns and epidemiologic shifts for conditions diagnosed and treated in emergency departments (EDs), especially for vulnerable populations. In addition, climate-driven intensification of extreme weather is disrupting health care delivery in EDs and health care systems. Thus, there are significant opportunities for emergency medicine to lead the medical response to climate change through 7 key areas: clinical practice improvements, building resilient EDs and health care systems, adaptation and public health engagement, disaster preparedness, mitigation, research, and education. In the face of this growing health threat, systemwide preparation rooted in local leadership and responsiveness is necessary to efficiently and effectively care for our vulnerable communities., (Copyright © 2020 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Background Pertussis is a highly contagious, vaccine-preventable respiratory disease. Historically, pertussis incidence was cyclic with peaks in disease every 3–5 years. In the United States, reported pertussis has increased over the past few decades despite high vaccination coverage; however, there is currently no clear national spatiotemporal pattern. We aimed to assess whether geographically distinct areas in the United States: (1) share similar temporal patterns (trend and periodicity), and (2) were synchronous in peaks in pertussis incidence. Methods We used pertussis cases reported through the National Notifiable Diseases Surveillance System, and CDC Wonder bridged-race county population estimates, for 2000–2017. County-level pertussis case counts were aggregated by month, and counties were aggregated into population areas of ≥300,000 persons. For each population area, trend and dominant periods across the study period were extracted using wavelet analysis. Common temporal patterns were identified using hierarchical cluster analysis of trend and periodicity. Synchrony between population area pairs, and between each area and the country as a whole, were assessed using wavelet coherence and phase difference. Results There was substantial variability in temporal patterns, though geographically distinct population areas clustered by trend and similar dominant periods of 8 to <19 months, 19 to <38 months, and 38 to 71 months, with three main patterns accounting for 79% (400/506) of all population areas (Figures 1 and 2). The majority of areas had a background period of at least 38 months, and 87% (439/506) of population areas experienced a positive trend. However, only 37% (185/506) of areas were synchronous with the national time series at any time during 2000–2017. Conclusion Spatiotemporal patterns in pertussis incidence are complex, and are heterogeneous across the United States. Although a background period of at least 38 months was identified in the majority of areas, similar to the historic perception of a 3–5-year cycle, higher frequency components were also identified. A better understanding of the current spatiotemporal patterns of pertussis will allow us to better characterize current epidemiology and improve prediction of future outbreaks. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Enterovirus D68 (EV-D68) causes worldwide outbreaks of human respiratory illness with spacio-temporally related outbreaks of acute flaccid myelitis (AFM), a polio-like illness. Numerous seroepidemiology studies show that nearly all humans older than 2 years have EV-D68-neutralizing antibodies in their serum, even in serum collected prior to large outbreaks. However, little else is known about the human antibody response to this virus. We sought to isolate human monoclonal antibodies (mAbs) from B cells in peripheral blood mononuclear cells (PBMCs) of immune subjects, induced by natural infection, to understand human humoral immunity to EV-D68. Methods We obtained PBMCs from donors with known infection during the largest ever recorded outbreak, which occurred in the United States in 2014. We used EV-D68 virus isolates from this outbreak in an indirect ELISA to screen immortalized PBMCs for antigen-specificity, then fused them with myeloma cells to create hybridomas. Results To date, we have isolated > 60 naturally occurring anti-EV-D68 human mAbs from the B cells of subjects with documented infection. These mAbs exhibit diverse binding affinities when compared across different clades of recent EV-D68 isolates. Many mAbs neutralize EV-D68 quite potently in vitro , with [ng/mL] half maximal effective concentrations. Some mAbs neutralize diverse clades of EV-D68, whereas others are highly clade-specific. Binding of antibodies to at least three, but likely more, major antigenic sites on the virus leads to neutralization. Conclusion We observed a qualitative difference among antibodies isolated from patients who had natural infection. These differences could contribute to certain individuals being susceptible to respiratory disease and AFM. Our studies of humoral immunity are especially important for a disease with nearly universal apparent seroprotection, in which the virus somehow persistently causes outbreaks across the world. Furthermore, no licensed vaccines or treatments exist for EV-D68. Given the ability of human intravenous immune globulin to protect mice from AFM, these mAbs are being tested for therapeutic benefit in vivo , and may have promise in the prevention and/or treatment of EV-D68-related diseases. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]