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COVID-19 Lead Time: Evaluating the timeliness and reliability of reported COVID-19 cases and hospitalizations as leading indicators of hospitalizations and death in the US

The COVID-19 pandemic prompted a reliance on real-time data sources to understand the global spread and impact of the SARS-CoV-2 virus. Reported cases were presumed leading indicators for hospitalizations, while hospitalizations were considered predictive of deaths. However, studies have questioned the consistency of reported cases as leading indicators. This study systematically assesses the reliability of United States (US) reported cases and hospitalizations as leading indicators for hospitalizations and deaths respectively, examining the first 2.5 years of the pandemic (January 2020 - June 2022) across different phases of the pandemic and states. Using correlation analysis, population data, and forecasting accuracy measures, we investigate the temporal relationships and identify possible determinants of lead time variability. Notably, we found that the average lead time between reported cases and hospitalizations across US states is relatively short at 1.76 days, implying that reported cases might not be as effective a leading indicator for hospitalizations as previously believed. Populations with higher comorbidity burdens, such as proportion of smokers, are expected on average to have shorter lead times, possibly due to shorter time to hospitalization among these vulnerable populations.

59 BASIC BIOLOGICAL SCIENCES↗

Evidence for persistent and shared bacterial strains against a background of largely unique gut colonization in hospitalized premature infants

The potentially critical stage of initial gut colonization in premature infants occurs in the hospital environment, where infants are exposed to a variety of hospital-associated bacteria. Because few studies of microbial communities are strain-resolved, we know little about the extent to which specific strains persist in the hospital environment and disperse among infants. To study this, we compared 304 near-complete genomes reconstructed from fecal samples of 21 infants hospitalized in the same intensive care unit in two cohorts, over 3 years apart. The genomes represent 159 distinct bacterial strains, only 14 of which occurred in multiple infants. Enterococcus faecalis and Staphylococcus epidermidis, common infant gut colonists, exhibit diversity comparable to that of reference strains, inline with introduction of strains from infant-specific sources rather than a hospital strain pool. Unlike other infants, a pair of sibling infants shared multiple strains, even after extensive antibiotic administration, suggesting overlapping strain-sources and/or genetic selection drive microbiota similarities. Interestingly, however, five strains were detected in infants hospitalized three years apart. Three of these were also detected in multiple infants in the same year. Finally, this finding of a few widely dispersed and persistent bacterial colonizers despite overall low potential for strain dispersal among infants has implications for understanding and directing healthy colonization.

60 APPLIED LIFE SCIENCES↗

Moving Beyond Mortality: Development and Application of a Desirability of Outcome Ranking (DOOR) Endpoint for Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia

Abstract Background Hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) are frequently caused by multidrug-resistant organisms. Patient-centered endpoints in clinical trials are needed to develop new antibiotics for HABP/VABP. Desirability of outcome ranking (DOOR) is a paradigm for the design, analysis, and interpretation of clinical trials based on a patient-centered, benefit-risk evaluation. Methods A multidisciplinary committee created an infectious diseases DOOR endpoint customized for HABP/VABP, incorporating infectious complications, serious adverse events, and mortality. We applied this to 2 previously completed, large randomized controlled trials for HABP/VABP. ZEPHyR compared vancomycin to linezolid and VITAL compared linezolid to tedizolid. For each trial, we evaluated the DOOR distribution and probability, including DOOR component and partial credit analyses. We also applied DOOR in subgroup analyses. Results In both trials, the HABP/VABP DOOR demonstrated similar overall clinical outcomes between treatment groups. In ZEPHyR, the probability that a participant treated with linezolid would have a more desirable outcome than a participant treated with vancomycin was 50.2% (95% confidence interval [CI], 45.1%­−55.3%). In VITAL, the probability that a participant treated with tedizolid would have a more desirable outcome than a participant treated with linezolid was 48.7% (95% CI, 44.8%–52.6%). The DOOR component analysis revealed that participants treated with tedizolid had a less desirable outcome than those treated with linezolid when considering clinical response alone. However, participants with decreased renal function had improved overall outcomes with tedizolid. Conclusions The HABP/VABP DOOR provided more granular information about clinical outcomes than is typically presented in clinical trials. HABP/VABP trials would benefit from prospectively using DOOR.

Immunology↗

GATEWAY Demonstrations: Tuning Hospital Lighting: Evaluating Tunable LED Lighting at the Swedish Hospital Behavioral Health Unit in Seattle

The GATEWAY program evaluated a tunable LED lighting system installed in the new Swedish Medical Behavioral Health Unit in Seattle that incorporates color-tunable luminaires in common areas, and uses advanced controls for dimming and color tuning, with the goal of providing a better environment for staff and patients. The report reviews the design of the tunable lighting system, summarizes two sets of measurements, and discusses the circadian, energy, and commissioning implications as well as lessons learned from the project.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

Control and prevention measures for legionellosis in hospitals: A cross-sectional survey in Italy

Highlights: • Legionellosis risk is high in Italian hospitals with many hospitalizations. • Legionella contamination in the water system was assessed in 97% of hospitals. • Risk assessment was performed in 73% of hospitals but only 53% had a dedicated team. • Measures to reduce legionellosis risk were adopted in 93.3% of hospitals. • Training courses on Legionnaires’ disease were planned in 36.5% of hospitals. Risk assessment, environmental monitoring, and the disinfection of water systems are the key elements in preventing legionellosis risk. The Italian Study Group of Hospital Hygiene of the Italian Society of Hygiene, Preventive Medicine, and Public Health and the Italian Multidisciplinary Society for the Prevention of Health Care-Associated Infections carried out a national cross-sectional survey to investigate the measures taken to prevent and control legionellosis in Italian hospitals. A multiple-choice questionnaire was developed, comprising 71 questions regarding hospital location, general characteristics, clinical and environmental surveillance, and control and preventive measures for legionellosis in 2015. Overall, 739 hospitals were enrolled from February to June 2017, and 178 anonymous questionnaires were correctly completed and evaluated (response rate: 24.1%). The survey was conducted using the SurveyMonkey® platform, and the data were analyzed using Stata 12 software. Of the participating hospitals, 63.2% reported at least one case of legionellosis, of which 28.2% were of proven nosocomial origin. The highest case numbers were reported in the Northern Italy, in hospitals with a pavilion structure or cooling towers, and in hospitals with higher numbers of beds, wards and operating theaters. Laboratory diagnosis was performed using urinary antigen testing alone (31.9%), both urinary antigen testing and single antibody titer (17.8%), or with seroconversion also added (21.5%). Culture-based or molecular investigations were performed in 28.8% and 22.1% of the clinical specimens, respectively. The water systems were routinely tested for Legionella in 97.4% of the hospitals, 62% of which detected a positive result (> 1000 cfu/L). Legionella pneumophila serogroup 2–15 was the most frequently isolated species (58.4%). The most common control measures were the disinfection of the water system (73.7%), mostly through thermal shock (37.4%) and chlorine dioxide (34.4%), and the replacement (69.7%) or cleaning (70.4%) of faucets and showerheads. A dedicated multidisciplinary team was present in 52.8% of the hospitals, and 73% of the hospitals performed risk assessment. Targeted training courses were organized in 36.5% of the hospitals, involving nurses (30.7%), physicians (28.8%), biologists (21.5%), technicians (26.4%), and cleaners (11%). Control and prevention measures for legionellosis are present in Italian hospitals, but some critical aspects should be improved. More appropriate risk assessment is necessary, especially in large facilities with a high number of hospitalizations. Moreover, more sensitive diagnostic tests should be used, and dedicated training courses should be implemented.

54 ENVIRONMENTAL SCIENCES↗

Why Travel for Complex Cancer Surgery? Americans React to ‘Brand-Sharing’ Between Specialty Cancer Hospitals and Their Affiliates

Introduction: Leading cancer hospitals have increasingly shared their ‘brand’ with smaller hospitals through affiliations. Because each brand evokes a distinct reputation for the care provided, ‘brand-sharing’ has the potential to impact the public’s ability to differentiate the safety and quality within hospital networks. The general public was surveyed to determine the perceived similarities and differences in the safety and quality of complex cancer surgery performed at top cancer hospitals and their smaller affiliate hospitals. Methods: A national, web-based KnowledgePanel (GfK) survey of American adults was conducted. Respondents were asked about their beliefs regarding the quality and safety of complex cancer surgery at a large, top-ranked cancer hospital and a smaller, local hospital, both in the presence and absence of an affiliation between the hospitals. Results: A total of 1010 surveys were completed (58.1% response rate). Overall, 85% of respondents felt ‘motivated’ to travel an hour for complex surgery at a larger hospital specializing in cancer, over a smaller local hospital. However, if the smaller hospital was affiliated with a top-ranked cancer hospital, 31% of the motivated respondents changed their preference to the smaller hospital. When asked to compare leading cancer hospitals and their smaller affiliates, 47% of respondents felt that surgical safety, 66% felt guideline compliance, and 53% felt cure rates would be the same at both hospitals. Conclusions: Approximately half of surveyed Americans did not distinguish the quality and safety of surgical care at top-ranked cancer hospitals from their smaller affiliates, potentially decreasing their motivation to travel to top centers for complex surgical care.

60 APPLIED LIFE SCIENCES↗

Declines in Pneumonia and Meningitis Hospitalizations in Children Under 5 Years of Age After Introduction of 10-Valent Pneumococcal Conjugate Vaccine in Zambia, 2010–2016

Background: Pneumococcus is a leading cause of pneumonia and meningitis. Zambia introduced a 10-valent pneumococcal conjugate vaccine (PCV10) in July 2013 using a 3-dose primary series at ages 6, 10, and 14 weeks with no booster. We evaluated the impact of PCV10 on meningitis and pneumonia hospitalizations. Methods: Using hospitalization data from first-level care hospitals, available at the Ministry of Health, and from the largest pediatric referral hospital in Lusaka, we identified children aged <5 years who were hospitalized with pneumonia or meningitis from January 2010–December 2016. We used time-series analyses to measure the effect of PCV10 on monthly case counts by outcome and age group (<1 year, 1–4 years), accounting for seasonality. We defined the pre- and post-PCV10 periods as January 2010–June 2013 and July 2014–December 2016, respectively. Results: At first-level care hospitals, pneumonia and meningitis hospitalizations among children aged <5 years accounted for 108 884 and 1742 admissions in the 42 months pre-PCV10, respectively, and 44 715 and 646 admissions in the 30 months post-PCV10, respectively. Pneumonia hospitalizations declined by 37.8% (95% confidence interval [CI] 21.4–50.3%) and 28.8% (95% CI 17.7–38.7%) among children aged <1 year and 1–4 years, respectively, while meningitis hospitalizations declined by 72.1% (95% CI 63.2–79.0%) and 61.6% (95% CI 50.4–70.8%), respectively, in these age groups. In contrast, at the referral hospital, pneumonia hospitalizations remained stable and a smaller but significant decline in meningitis was observed among children aged 1–4 years (39.3%, 95% CI 16.2–57.5%). Conclusions: PCV10 introduction was associated with declines in meningitis and pneumonia hospitalizations in Zambia, especially in first-level care hospitals.

59 BASIC BIOLOGICAL SCIENCES↗

PM10 exposure is associated with increased hospitalizations for respiratory syncytial virus bronchiolitis among infants in Lombardy, Italy

Highlights: • Respiratory syncytial virus bronchiolitis (RSV-B) might be influenced by air pollution. • PM10 was associated with RSV-B hospitalizations among infants in Lombardy, Italy. • The most relevant exposure windows were the 2 weeks preceding hospitalization. Respiratory syncytial virus (RSV) is the primary cause of acute lower respiratory infections in children, bronchiolitis in particular. Airborne particulate matter (PM) may influence the children's immune system and foster the spread of RSV infection. We aimed to verify whether PM10 exposure is associated with hospitalization due to RSV bronchiolitis. We selected hospital discharge records (HRD) with ICD-9-CM code 466.11 of infants < 1 year of age, occurring in the epidemic seasons of two years (2012–2013) in Lombardy, Italy. Cases were assigned daily PM10 and apparent temperature levels of the capital city of their residential province. Different exposure windows were considered: single days preceding hospitalization (lag 0 to 30), their average estimates (lag 0–1 to 0–30), and the four weeks preceding hospitalization (week 1 to 4). Negative binomial regression models adjusted for apparent temperature and season were applied to the daily counts of hospitalizations in each province. Results were expressed as incidence rate ratios (IRR) and 95% confidence intervals (95%CI) per 10 µg/m{sup 3} increase in PM10 concentration. Random effects meta-analyses of province-specific IRR were performed to obtain regional estimates. 2814 HRD met our inclusion criteria; males represented about 55% of the cases. A 6% increased risk of hospitalization (95%CI: 1.03–1.10) was found at lag 0 and an almost overlapping 7% increase at lag 1. IRR ranged from 1.03 to 1.05 between lags 2 and 11. No increased risk was observed from lag 12. When considering averaged daily lags, risk estimates gradually increased in the two weeks preceding hospitalization from 1.08 (1.04–1.12) at lag 0–1 to 1.15 (1.08–1.23) between lags 0–11 and 0–13. Analyses on weekly lags showed a risk increase of 6% (1.01–1.12) during week 1 and of 7% (1.02–1.13) during week 2. Our study found a clear association between short- and medium-term PM10 exposures and increased risk of hospitalization due to RSV bronchiolitis among infants.

54 ENVIRONMENTAL SCIENCES↗

Prescribed fires, smoke exposure, and hospital utilization among heart failure patients

Abstract Background Prescribed fires often have ecological benefits, but their environmental health risks have been infrequently studied. We investigated associations between residing near a prescribed fire, wildfire smoke exposure, and heart failure (HF) patients’ hospital utilization. Methods We used electronic health records from January 2014 to December 2016 in a North Carolina hospital-based cohort to determine HF diagnoses, primary residence, and hospital utilization. Using a cross-sectional study design, we associated the prescribed fire occurrences within 1, 2, and 5 km of the patients’ primary residence with the number of hospital visits and 7- and 30-day readmissions. To compare prescribed fire associations with those observed for wildfire smoke, we also associated zip code-level smoke density data designed to capture wildfire smoke emissions with hospital utilization amongst HF patients. Quasi-Poisson regression models were used for the number of hospital visits, while zero-inflated Poisson regression models were used for readmissions. All models were adjusted for age, sex, race, and neighborhood socioeconomic status and included an offset for follow-up time. The results are the percent change and the 95% confidence interval (CI). Results Associations between prescribed fire occurrences and hospital visits were generally null, with the few associations observed being with prescribed fires within 5 and 2 km of the primary residence in the negative direction but not the more restrictive 1 km radius. However, exposure to medium or heavy smoke (primarily from wildfires) at the zip code level was associated with both 7-day (8.5% increase; 95% CI = 1.5%, 16.0%) and 30-day readmissions (5.4%; 95% CI = 2.3%, 8.5%), and to a lesser degree, hospital visits (1.5%; 95% CI: 0.0%, 3.0%) matching previous studies. Conclusions Area-level smoke exposure driven by wildfires is positively associated with hospital utilization but not proximity to prescribed fires.

Raab, Henry↗

Identifying Sociomarkers of Pediatric Asthma Patients at Risk of Hospital Revisiting

ObjectiveAsthma is one of the most common chronic childhood diseases in the United States [2, 3]. In addition to its pervasiveness, pediatric asthma shows high sensitivity to the environment. Combining medical-social dataset with machine learning methods we demonstrate how socio-markers play an important role in identifying patients at risk of hospital revisits due to pediatric asthma within a year.IntroductionA socio-marker is a measurable indicator of social conditions where a patient is embedded in and exposed to, being analogous with a biomarker indicating the severity or presence of some disease state. Social factors are one of the most clinical health determinants [1], which play a critical role in explaining health outcomes. Socio-markers can help medical practitioners and researchers to reliably identify high-risk individuals in a timely manner.MethodsWe collected data from three different sources: pediatric asthma encounter records from Jan 1st, 2016 to Dec 31st, 2016 at a children’s hospital, the 2010 U.S census data and neighborhood quality survey data by Memphis Property Hub. After merging these datasets we examine the effect of social features in identifying the patients who visited the hospital more than once during the observation period. We only use the first time visit (3,678 cases) to avoid over-counting of the same patients. In addition to demographic features (age, gender, insurance type, and race (African American and White)), we incorporate the social features such as the proportion of individuals living below the federal poverty level, blight prevalence, neighborhood quality, neighborhood quality inequality, trash dumping presence, the broken window pervasiveness within the zip code area of patients’ residence are included.We then implemented a Support Vector Machine (SVM) based classification model using abovementioned 11 social features. The classification outcome is either patient visits the hospital only one-time (class 0) or revisits the hospital within a year (class 1). Among 3,678 unique patients in the dataset, only 823 pediatric patients revisited hospital with asthma. So, to overcome the class imbalance issue, we have used 823 patients’ data (randomly selected in 1,000 iterations) from each class. Further, to avoid overfitting and ensure generalizability, we divided the dataset as training, test, and validation with a proportion of 60%, 20%, and 20%, respectively. The reported test (5-folds cross-validation using training and testing data) and validation accuracy of the SVM method are averaged over 1,000 iterations to avoid sampling error and bias.ResultsThe proposed socio-marker model resulted in an average classification accuracy of 63.70% for the test set and 63.67 % for the validation set. Further, the average specificity (the total true negative cases divided by the sum of true negative and false positive) and sensitivity (the total number of true positive cases divided by the sum of positive predicted cases) is found to be 62.79% and 64.77%, respectively for the test set and 62.79% and 64.83%, respectively for the validation set. Results of this study suggest that socio-marker features that are not directly related to a patient’s medical conditions can still predict whether the patient will come back to the hospital within a year or not with approximately 64% accuracy.ConclusionsBringing the socio-marker features in the surveillance system may ease the burden of detecting the patients at risk of revisiting the hospital. The results should be interpreted with caution because we only used 12-month period of observation and the visit beyond the observation window is not considered. Also the patients may have visited different hospitals which are not captured in the data.References1. Booske BC, Athens JK, Kindig DA, Park H, Remington PL: Different perspectives for assigning weights to determinants of health. University of Wisconsin: Population Health Institute 2010.2. Subbarao P, Mandhane PJ, Sears MR: Asthma: epidemiology, etiology and risk factors. Canadian Medical Association Journal 2009, 181(9):E181-E190.3. Gold DR, Wright R: Population disparities in asthma. Annu Rev Public Health 2005, 26:89-113.

Shin, Eun Kyong↗

The Impact of Intensity Modulated Radiation Therapy on Hospitalization Outcomes in the SEER-Medicare Population With Anal Squamous Cell Carcinoma

Purpose: We examined the impact of intensity modulated radiation therapy (IMRT) on hospitalization rates in the Surveillance, Epidemiology, and End Results (SEER)–Medicare population with anal squamous cell carcinoma (SCC). Methods and Materials: We performed a retrospective cohort study using the SEER-Medicare database. We identified patients with nonmetastatic anal SCC diagnosed between 2001 and 2011 and treated with chemoradiation therapy. We assessed the relation between IMRT and first hospitalization by use of a multivariate competing-risk model, as well as instrumental variable analysis, using provider IMRT affinity as our instrument. Results: Of the 1165 patients included in our study, 458 (39%) received IMRT. IMRT use increased over time and was associated more with regional and provider characteristics than with patient characteristics. The 3- and 6-month cumulative incidences of first hospitalization were 41.9% (95% confidence interval [CI], 37.3%-46.4%) and 47.6% (95% CI, 43.0%-52.2%), respectively, for the IMRT cohort and 46.7% (95% CI, 43.0%-50.4%) and 52.1% (95% CI, 48.4%-55.7%), respectively, for the non-IMRT cohort. IMRT was associated with a decreased hazard of first hospitalization compared with 3-dimensional radiation techniques (hazard ratio, 0.70; 95% CI, 0.58-0.84; P=.0002). Instrumental variable analysis suggested an even greater reduction in hospitalizations with IMRT after controlling for unmeasured confounders. There was a trend toward improved overall survival with IMRT, with an adjusted hazard ratio of 0.77 (95% CI, 0.59-1.00; P=.05). Conclusions: The use of IMRT is associated with reduced hospitalizations in elderly patients with anal SCC. Further work is warranted to understand the long-term health and cost impact of IMRT, particularly for patient subgroups most at risk of toxicity and hospitalization.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Anomaly Detection in Electronic Health Records Across Hospital Networks: Integrating Machine Learning With Graph Algorithms

In a large hospital system, a network of hospitals relies on electronic health records (EHRs) to make informed decisions regarding their patients in various clinical domains. Consequently, the dependability of the health information technology (HIT) systems responsible for collecting EHR data is of utmost importance for patient safety. Recently, novel methods and tools aimed at identifying anomalies in EHR data to bolster the reliability of HIT systems have been introduced. However, these existing methods and tools primarily concentrate on individual hospitals, which limits our understanding of system-wide anomalous events and their potential impact on patient safety across multiple hospitals. In this article, we introduce a new approach to detecting anomalies in EHR data within a network of hospitals. This is achieved by combining advanced machine learning techniques with graph algorithms to create a tool capable of swiftly identifying and responding to deviations. Our proposed approach employs a combination of five machine learning models, harnessing the unique strengths of each model to provide a more robust detection system. The detected anomalies are then represented as graphs, allowing us to recognize patterns across the hospital network. This aids in identifying anomalies that span multiple medical facilities, potentially indicating broader system-level risks. Extensive real-world testing of our approach demonstrated its ability to offer actionable insights compared to existing methods. Additionally, its scalable design ensures seamless integration into existing HIT infrastructures.

Niu, Haoran [Oak Ridge National Laboratory (ORNL),↗

Assessment on security system of radioactive sources used in hospitals of Thailand

Unsecured radioactive sources have caused deaths and serious injuries in many parts of the world. In Thailand, there are 17 hospitals that use teletherapy with cobalt-60 radioactive sources. They need to be secured in order to prevent unauthorized removal, sabotage and terrorists from using such materials in a radiological weapon. The security system of radioactive sources in Thailand is regulated by the Office of Atoms for Peace in compliance with Global Threat Reduction Initiative (GTRI), U.S. DOE, which has started to be implemented since 2010. This study aims to perform an assessment on the security system of radioactive sources used in hospitals in Thailand and the results can be used as a recommended baseline data for development or improvement of hospitals on the security system of a radioactive source at a national regulatory level and policy level. Results from questionnaires reveal that in 11 out of 17 hospitals (64.70%), there were a few differences in conditions of hospitals using radioactive sources with installation of the security system and those without installation of the security system. Also, personals working with radioactive sources did not clearly understand the nuclear security law. Thus, government organizations should be encouraged to arrange trainings on nuclear security to increase the level of understanding. In the future, it is recommended that the responsible government organization issues a minimum requirement of nuclear security for every medical facility using radioactive sources.

07 ISOTOPE AND RADIATION SOURCES↗

Genome-resolved metagenomics of eukaryotic populations during early colonization of premature infants and in hospital rooms

Background: Fungal infections are a significant cause of mortality and morbidity in hospitalized preterm infants, yet little is known about eukaryotic colonization of infants and of the neonatal intensive care unit as a possible source of colonizing strains. This is partly because microbiome studies often utilize bacterial 16S rRNA marker gene sequencing, a technique that is blind to eukaryotic organisms. Knowledge gaps exist regarding the phylogeny and microdiversity of eukaryotes that colonize hospitalized infants, as well as potential reservoirs of eukaryotes in the hospital room built environment. Results: Genome-resolved analysis of 1174 time-series fecal metagenomes from 161 premature infants revealed fungal colonization of 10 infants. Relative abundance levels reached as high as 97% and were significantly higher in the first weeks of life (p = 0.004). When fungal colonization occurred, multiple species were present more often than expected by random chance (p = 0.008). Twenty-four metagenomic samples were analyzed from hospital rooms of six different infants. Compared to floor and surface samples, hospital sinks hosted diverse and highly variable communities containing genomically novel species, including from Diptera (fly) and Rhabditida (worm) for which genomes were assembled. With the exception of Diptera and two other organisms, zygosity of the newly assembled diploid eukaryote genomes was low. Interestingly, Malassezia and Candida species were present in both room and infant gut samples. Conclusions: Increased levels of fungal co-colonization may reflect synergistic interactions or differences in infant susceptibility to fungal colonization. Discovery of eukaryotic organisms that have not been sequenced previously highlights the benefit of genome-resolved analyses, and low zygosity of assembled genomes could reflect inbreeding or strong selection imposed by room conditions.

59 BASIC BIOLOGICAL SCIENCES↗

Association Between Changes in Timing of Spring Onset and Asthma Hospitalization in Maryland

The proposed association between climate change and increased burden of allergic diseases are based on three different thematic observational studies that have linked (i) increased CO 2 concentration with higher pollen production, (ii) warmer air/surface temperatures with early spring onset and longer pollen season, and (iii) higher pollen exposure with increased risk of asthma hospitalizations. Yet empirical evidence collectively linking climate change with pollen season and asthma exacerbation is still lacking. Using satellite observations, in situ pollen monitoring data, and hospitalization records (2001-2012), here we show that changes in the timing of spring onset resulting from ongoing climate variability and change is directly related to a longer tree pollen season and increased risk of asthma hospitalization. More specifically, we observed that very early start of season (SOS) to be associated with 10% increase in risk of asthma hospitalization (Incident Rate Ratio (IRR): 1.10, 95% Confidence Interval (CI): 1.02- 1.20) while late onset of SOS to be associated with 3% increase in risk of asthma hospitalization in Maryland (IRR: 1.03, 95% CI: 0.97-1.11), however the risk in the latter case was not statistically significant. Our results serve as a wake-up call to public health and medical communities regarding the need to anticipate and adapt to the ongoing changes in the timing and severity of the spring allergy season.

54 ENVIRONMENTAL SCIENCES↗

Cartography of opportunistic pathogens and antibiotic resistance genes in a tertiary hospital environment

Although disinfection is key to infection control, the colonization patterns and resistomes of hospital-environment microbes remain underexplored. We report the first extensive genomic characterization of microbiomes, pathogens and antibiotic resistance cassettes in a tertiary-care hospital, from repeated sampling (up to 1.5 years apart) of 179 sites associated with 45 beds. Deep shotgun metagenomics unveiled distinct ecological niches of microbes and antibiotic resistance genes characterized by biofilm-forming and human-microbiome-influenced environments with corresponding patterns of spatiotemporal divergence. Quasi-metagenomics with nanopore sequencing provided thousands of high-contiguity genomes, phage and plasmid sequences (>60% novel), enabling characterization of resistome and mobilome diversity and dynamic architectures in hospital environments. Phylogenetics identified multidrug-resistant strains as being widely distributed and stably colonizing across sites. Comparisons with clinical isolates indicated that such microbes can persist in hospitals for extended periods (>8 years), to opportunistically infect patients. These findings highlight the importance of characterizing antibiotic resistance reservoirs in hospitals and establish the feasibility of systematic surveys to target resources for preventing infections.

59 BASIC BIOLOGICAL SCIENCES↗

Pharmacoepidemiology, Machine Learning and COVID-19: An intent-to-treat analysis of hydroxychloroquine, with or without azithromycin, and COVID-19 outcomes amongst hospitalized US Veterans

Hydroxychloroquine (HCQ) was proposed as an early therapy for coronavirus disease 2019 (COVID-19) after in vitro studies indicated possible benefit. Previous in vivo observational studies have presented conflicting results, though recent randomized clinical trials have reported no benefit from HCQ amongst hospitalized COVID-19 patients. In this work, we examined the effects of HCQ alone, and in combination with azithromycin, in a hospitalized COVID-19 positive, United States (US) Veteran population using a propensity score adjusted survival analysis with imputation of missing data. From March 1, 2020 through April 30, 2020, 64,055 US Veterans were tested for COVID-19 based on Veteran Affairs Healthcare Administration electronic health record data. Of the 7,193 positive cases, 2,809 were hospitalized, and 657 individuals were prescribed HCQ within the first 48-hours of hospitalization for the treatment of COVID-19. There was no apparent benefit associated with HCQ receipt, alone or in combination with azithromycin, and an increased risk of intubation when used in combination with azithromycin [Hazard Ratio (95% Confidence Interval): 1.55 (1.07, 2.24)]. In conclusion, we assessed the effectiveness of HCQ with or without azithromycin in treating patients hospitalized with COVID-19 using a national sample of the US Veteran population. Using rigorous study design and analytic methods to reduce confounding and bias, we found no evidence of a survival benefit from the administration of HCQ.

60 APPLIED LIFE SCIENCES↗