ATF4 and mTOR regulate metabolic reprogramming in TGF-ß-treated lung fibroblasts.

Idiopathic pulmonary fibrosis is a fatal disease characterized by the TGF-ß-dependent activation of lung fibroblasts, leading to excessive deposition of collagen proteins and progressive replacement of healthy lung with scar tissue. We and others have shown that fibroblast activation is supported by metabolic reprogramming, including the upregulation of the de novo synthesis of glycine, the most abundant amino acid found in collagen protein. How fibroblast metabolic reprogramming is regulated downstream of TGF-ß is incompletely understood. We and others have shown that TGF-ß-mediated activation of the Mechanistic Target of Rapamycin Complex 1 (mTORC1) and downstream upregulation of Activating Transcription Factor 4 (ATF4) promote increased expression of the enzymes required for de novo glycine synthesis; however, whether mTOR and ATF4 regulate other metabolic pathways in lung fibroblasts has not been explored. Here, we used RNA sequencing to determine how both ATF4 and mTOR regulate gene expression in human lung fibroblasts following TGF-ß. We found that ATF4 primarily regulates enzymes and transporters involved in amino acid homeostasis as well as aminoacyl-tRNA synthetases. mTOR inhibition resulted not only in the loss of ATF4 target gene expression, but also in the reduced expression of glycolytic enzymes and mitochondrial electron transport chain subunits. Analysis of TGF-ß-induced changes in cellular metabolite levels confirmed that ATF4 regulates amino acid homeostasis in lung fibroblasts while mTOR also regulates glycolytic and TCA cycle metabolites. We further analyzed publicly available single cell RNAseq data sets and found increased expression of ATF4 and mTOR metabolic targets in pathologic fibroblast populations from the lungs of IPF patients. Our results provide insight into the mechanisms of metabolic reprogramming in lung fibroblasts and highlight novel ATF4 and mTOR-dependent pathways that may be targeted to inhibit fibrotic processes.

A Six-Year Follow-Up of Bloodstream Infections in Hemodialysis Facilities in the United States, National Healthcare Safety Network, 2020.

METHODS: Outpatient hemodialysis facilities report BSI events to NHSN. Pooled mean rates with 95% CI were calculated overall and for each type of vascular access (arteriovenous (AV) fistula, AV graft, or a central venous catheter (CVC)). Standardized infection ratios were calculated as observed BSI events divided by the predicted number of events based on national aggregate data. Median facility-level standardized infection ratios and 95% confidence intervals (CIs) were stratified by state and US territory. RESULTS: During 2020, 7,183 outpatient hemodialysis facilities reported data for 5,235,234 patient months with 15,181 BSI events. Pooled mean rates per 100 person-months were 0.29 (95% CI, 0.29-0.30) overall, 0.80 (95% CI, 0.78-0.82) for CVC, 0.12 (95% CI, 0.12-0.12) for AV fistula, 0.21 (95% CI, 0.20-0.22) for AV graft, and 0.28 (95% CI, 0.19-0.40) for other access types. The national standardized infection ratio was 0.40 (95% CI, 0.39-0.41). South Dakota had a standardized infection ratio significantly higher than one (1.34; 95% CI, 1.11 - 1.62). Fifty-one of 54 states and territories had BSI standardized infection ratio significantly lower than one. CONCLUSIONS: In 2020, the median standardized infection ratio for BSI in US outpatient hemodialysis facilities was lower than predicted overall and in almost all states and territories. An elevated standardized infection ratio was identified in South Dakota.

Intrusive Traumatic Re-Experiencing Domain: Functional Connectivity Feature Classification by the ENIGMA PTSD Consortium.

Background: Intrusive traumatic re-experiencing domain (ITRED) was recently introduced as a novel perspective on posttraumatic psychopathology, proposing to focus research of posttraumatic stress disorder (PTSD) on the unique symptoms of intrusive and involuntary re-experiencing of the trauma, namely, intrusive memories, nightmares, and flashbacks. The aim of the present study was to explore ITRED from a neural network connectivity perspective. Methods: Data were collected from 9 sites taking part in the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) PTSD Consortium (n= 584) and included itemized PTSD symptom scores and resting-state functional connectivity (rsFC) data. We assessed the utility of rsFC in classifying PTSD, ITRED-only (no PTSD diagnosis), and trauma-exposed (TE)-only (no PTSD or ITRED) groups using a machine learning approach, examining well-known networks implicated in PTSD. A random forest classification model was built on a training set using cross-validation, and the averaged cross-validation model performance for classification was evaluated using the area under the curve. The model was tested using a fully independent portion of the data (test dataset), and the test area under the curve was evaluated. Results: rsFC signatures differentiated TE-only participants from PTSD and ITRED-only participants at about 60% accuracy. Conversely, rsFC signatures did not differentiate PTSD from ITRED-only individuals (45% accuracy). Common features differentiating TE-only participants from PTSD and ITRED-only participants mainly involved default mode network-related pathways. Some unique features, such as connectivity within the frontoparietal network, differentiated TE-only participants from one group (PTSD or ITRED-only) but to a lesser extent from the other group. Conclusions: Neural network connectivity supports ITRED as a novel neurobiologically based approach to classifying posttrauma psychopathology.

An Update From the National Healthcare Safety Network on Hospital Antibiotic Stewardship Programs in the United States, 2014-2021.

Background: In 2014, the Centers for Disease Control and Prevention (CDC) released the Core Elements of Hospital Antibiotic Stewardship Programs (ASPs) and began monitoring uptake through the National Healthcare Safety Network (NHSN) Annual Hospital Survey. In 2019, CDC updated the Core Elements and in 2022 released the Priorities for Hospital Core Element Implementation. We describe Core Element uptake from 2014 to 2021, provide a snapshot of specific ASP practices in acute care hospitals in 2021, and describe how we plan to monitor stewardship moving forward. Methods: We used the NHSN Annual Hospital Survey to summarize facility demographics and ASP practices and to monitor uptake of Core Elements. Questions have been updated over time, so not all data could be compared across years. Results: Uptake of all 7 Core Elements increased from 41% in 2014 to 95% in 2021. Uptake of all 6 Priority Elements was 10% in 2021, though 46% of hospitals met 4 or 5 of the possible 6 elements. Antibiotic stewardship was specifically listed in a contract or job description for about 60% of program leaders. The percentage of physician-pharmacist co-led programs rose from 23% to 64%. Seventy-six percent of hospitals reported implementing audit with feedback interventions. Conclusions: With nearly all acute care hospitals reporting uptake of the 7 Core Elements in 2021, and with more evidence for which ASP practices are most effective, the Priorities for Hospital Core Element Implementation were released in 2022 to help enhance the quality and impact of existing ASPs.

Impact of the COVID-19 Pandemic on Inpatient Antibiotic Use in the United States, January 2019 Through July 2022.

Antimicrobial use data reported to the National Healthcare Safety Network's Antimicrobial Use and Resistance Module between January 2019 and July 2022 were analyzed to assess the impact of the COVID-19 pandemic on inpatient antimicrobial use.

Vital Signs: Health Disparities in Hemodialysis-Associated Staphylococcus aureus Bloodstream Infections - United States, 2017-2020.

INTRODUCTION: Racial and ethnic minorities are disproportionately affected by end-stage kidney disease (ESKD). ESKD patients on dialysis are at increased risk for Staphylococcus aureus bloodstream infections, but racial, ethnic, and socioeconomic disparities associated with this outcome are not well described. METHODS: Surveillance data from the 2020 National Healthcare Safety Network (NHSN) and the 2017-2020 Emerging Infections Program (EIP) were used to describe bloodstream infections among patients on hemodialysis (hemodialysis patients) and were linked to population-based data sources (CDC/Agency for Toxic Substances and Disease Registry [ATSDR] Social Vulnerability Index [SVI], United States Renal Data System [USRDS], and U.S. Census Bureau) to examine associations with race, ethnicity, and social determinants of health. RESULTS: In 2020, 4,840 dialysis facilities reported 14,822 bloodstream infections to NHSN; 34.2% were attributable to S. aureus . Among seven EIP sites, the S. aureus bloodstream infection rate during 2017-2020 was 100 times higher among hemodialysis patients (4,248 of 100,000 person-years) than among adults not on hemodialysis (42 of 100,000 person-years). Unadjusted S. aureus bloodstream infection rates were highest among non-Hispanic Black or African American (Black) and Hispanic or Latino (Hispanic) hemodialysis patients. Vascular access via central venous catheter was strongly associated with S. aureus bloodstream infections (NHSN: adjusted rate ratio [aRR] = 6.2; 95% CI = 5.7-6.7 versus fistula; EIP: aRR = 4.3; 95% CI = 3.9-4.8 versus fistula or graft). Adjusting for EIP site of residence, sex, and vascular access type, S. aureus bloodstream infection risk in EIP was highest in Hispanic patients (aRR = 1.4; 95% CI = 1.2-1.7 versus non-Hispanic White [White] patients), and patients aged 18-49 years (aRR = 1.7; 95% CI = 1.5-1.9 versus patients aged ≥65 years). Areas with higher poverty levels, crowding, and lower education levels accounted for disproportionately higher proportions of hemodialysis-associated S. aureus bloodstream infections. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Disparities exist in hemodialysis-associated S. aureus infections. Health care providers and public health professionals should prioritize prevention and optimized treatment of ESKD, identify and address barriers to lower-risk vascular access placement, and implement established best practices to prevent bloodstream infections.

Vital Signs: Health Disparities in Hemodialysis-Associated Staphylococcus aureus Bloodstream Infections - United States, 2017-2020.

Introduction: Racial and ethnic minorities are disproportionately affected by end-stage kidney disease (ESKD). ESKD patients on dialysis are at increased risk for Staphylococcus aureus bloodstream infections, but racial, ethnic, and socioeconomic disparities associated with this outcome are not well described. Methods: Surveillance data from the 2020 National Healthcare Safety Network (NHSN) and the 2017-2020 Emerging Infections Program (EIP) were used to describe bloodstream infections among patients on hemodialysis (hemodialysis patients) and were linked to population-based data sources (CDC/Agency for Toxic Substances and Disease Registry [ATSDR] Social Vulnerability Index [SVI], United States Renal Data System [USRDS], and U.S. Census Bureau) to examine associations with race, ethnicity, and social determinants of health. Results: In 2020, 4,840 dialysis facilities reported 14,822 bloodstream infections to NHSN; 34.2% were attributable to S. aureus. Among seven EIP sites, the S. aureus bloodstream infection rate during 2017-2020 was 100 times higher among hemodialysis patients (4,248 of 100,000 person-years) than among adults not on hemodialysis (42 of 100,000 person-years). Unadjusted S. aureus bloodstream infection rates were highest among non-Hispanic Black or African American (Black) and Hispanic or Latino (Hispanic) hemodialysis patients. Vascular access via central venous catheter was strongly associated with S. aureus bloodstream infections (NHSN: adjusted rate ratio [aRR] = 6.2; 95% CI = 5.7-6.7 versus fistula; EIP: aRR = 4.3; 95% CI = 3.9-4.8 versus fistula or graft). Adjusting for EIP site of residence, sex, and vascular access type, S. aureus bloodstream infection risk in EIP was highest in Hispanic patients (aRR = 1.4; 95% CI = 1.2-1.7 versus non-Hispanic White [White] patients), and patients aged 18-49 years (aRR = 1.7; 95% CI = 1.5-1.9 versus patients aged ≥65 years). Areas with higher poverty levels, crowding, and lower education levels accounted for disproportionately higher proportions of hemodialysis-associated S. aureus bloodstream infections. Conclusions and implications for public health practice: Disparities exist in hemodialysis-associated S. aureus infections. Health care providers and public health professionals should prioritize prevention and optimized treatment of ESKD, identify and address barriers to lower-risk vascular access placement, and implement established best practices to prevent bloodstream infections.

First peripheral drug-eluting stent clinical results from China: 1-year outcomes of the Zilver PTX China study.

Purpose: The benefit of using the Zilver PTX drug-eluting stent (DES) in superficial femoral artery (SFA) lesions has been demonstrated in multiple clinical studies. This prospective, multicenter study evaluated the 1-year safety and effectiveness of the DES for the treatment of femoropopliteal lesions in a Chinese patient population. Methods: Patients with a single de novo or restenotic SFA lesion ≤140 mm and a Rutherford classification of 2 to 4 were treated with the DES. The primary endpoint was primary patency assessed by duplex ultrasound at 1-year. Secondary endpoints included adverse events, event-free survival (EFS), and freedom from target lesion revascularization (TLR). Clinical outcomes included Rutherford classification, ankle-brachial index (ABI), and the walking impairment questionnaire (WIQ). Results: In this study, 178 patients with symptomatic peripheral artery disease were enrolled at nine institutions in China. The average lesion length was 79.0 ± 48.6 mm (range 14.8-245.4 mm) and 50.0% of lesions were total occlusions. The 1-year primary patency rate was 81.9%. Covariate analysis revealed that lesion length (p < 0.01) was the only significant factor for patency. No paclitaxel-related adverse events or amputations were reported. The 1-year rate for EFS was 94.9% and freedom from TLR was 95.5%. Through 1-year, treatment with the DES resulted in statistically significant improvement in ABI and WIQ scores compared with pre-procedure (p < 0.001). Clinical improvement of at least 1 Rutherford class was achieved in 142 of 174 patients (81.6%). Conclusion: This study showed promising short-term results for the treatment of SFA lesions with Zilver PTX DES in Chinese patients. Unique identifier: ClinicalTrials.gov, identifier: NCT02171962.

Prevalence, increase and predictors of family violence during the COVID-19 pandemic, using modern machine learning approaches.

Background: We are facing an ongoing pandemic of coronavirus disease 2019 (COVID-19), which is causing detrimental effects on mental health, including disturbing consequences on child maltreatment and intimate partner violence. Methods: We sought to identify predictors of child maltreatment and intimate partner violence from 380 participants (mean age 36.67 ± 10.61, 63.2% male; Time 3: June 2020) using modern machine learning analysis (random forest and SHAP values). We predicted that COVID-related factors (such as days in lockdown), parents' psychological distress during the pandemic (anxiety, depression), their personality traits, and their intimate partner relationship will be key contributors to child maltreatment. We also examined if there is an increase in family violence during the pandemic by using an additional cohort at two time points (Time 1: March 2020, N = 434; mean age 35.67 ± 9.85, 41.69% male; and Time 2: April 2020, N = 515; mean age 35.3 ± 9.5, 34.33%). Results: Feature importance analysis revealed that parents' affective empathy, psychological well-being, outdoor activities with children as well as a reduction in physical fights between partners are strong predictors of a reduced risk of child maltreatment. We also found a significant increase in physical punishment (Time 3: 66.26%) toward children, as well as in physical (Time 3: 36.24%) and verbal fights (Time 3: 41.08%) among partners between different times. Conclusion: Using modernized predictive algorithms, we present a spectrum of features that can have influential weight on prediction of child maltreatment. Increasing awareness about family violence consequences and promoting parenting programs centered around mental health are imperative.

A comparison of methods to harmonize cortical thickness measurements across scanners and sites.

Results of neuroimaging datasets aggregated from multiple sites may be biased by site-specific profiles in participants' demographic and clinical characteristics, as well as MRI acquisition protocols and scanning platforms. We compared the impact of four different harmonization methods on results obtained from analyses of cortical thickness data: (1) linear mixed-effects model (LME) that models site-specific random intercepts (LMEINT), (2) LME that models both site-specific random intercepts and age-related random slopes (LMEINT+SLP), (3) ComBat, and (4) ComBat with a generalized additive model (ComBat-GAM). Our test case for comparing harmonization methods was cortical thickness data aggregated from 29 sites, which included 1,340 cases with posttraumatic stress disorder (PTSD) (6.2-81.8 years old) and 2,057 trauma-exposed controls without PTSD (6.3-85.2 years old). We found that, compared to the other data harmonization methods, data processed with ComBat-GAM was more sensitive to the detection of significant case-control differences (Χ2(3) = 63.704, p < 0.001) as well as case-control differences in age-related cortical thinning (Χ2(3) = 12.082, p = 0.007). Both ComBat and ComBat-GAM outperformed LME methods in detecting sex differences (Χ2(3) = 9.114, p = 0.028) in regional cortical thickness. ComBat-GAM also led to stronger estimates of age-related declines in cortical thickness (corrected p-values < 0.001), stronger estimates of case-related cortical thickness reduction (corrected p-values < 0.001), weaker estimates of age-related declines in cortical thickness in cases than controls (corrected p-values < 0.001), stronger estimates of cortical thickness reduction in females than males (corrected p-values < 0.001), and stronger estimates of cortical thickness reduction in females relative to males in cases than controls (corrected p-values < 0.001). Our results support the use of ComBat-GAM to minimize confounds and increase statistical power when harmonizing data with non-linear effects, and the use of either ComBat or ComBat-GAM for harmonizing data with linear effects.

The impact of preoperative imaging on wait times, surgical approach and overall survival in endometrioid endometrial cancers.

OBJECTIVES: Routine preoperative axial imaging studies (CT/MRI) are not recommended for endometrioid endometrial cancer as they are unlikely to change management and may delay surgery. This study evaluated the association of receiving preoperative imaging on various outcomes. METHODS: A population-based cohort of Endometrioid Endometrial Cancer cases from 2006 to 2016 were identified from the Cancer Registry in Ontario, Canada. Wait time to surgery, type of surgery and overall survival were evaluated in patients with and without preoperative imaging. Predictive factors for wait time > 56 days and aggressive surgery (radical hysterectomy / lymphadenectomy) were determined using multivariable regression analysis. RESULTS: 13,050 cases were included. 22.6% of patients received preoperative imaging, mainly CT scans. Most patients (95.9%) received no neoadjuvant treatment. Patients with preoperative imaging were more likely to have neoadjuvant treatment (11.7% vs. 1.8%) and less likely to have surgery at 180 days post diagnosis (87.9% vs 94.6%). Patients with preoperative imaging had median wait time to surgery of 64 days (47-87), compared to 53 days (36-74) than those without imaging (p < 0.001). Multivariable modeling showed preoperative imaging was associated with decreased odds of having surgery within 56 days (OR = 0.68, 95% CI = 0.62-0.75), and increased odds (OR = 1.73, 95% CI = 1.53-1.95) of having aggressive surgery. The 5-year overall survival for patients with imaging was 84.8% versus 91.1% for patients without preoperative imaging. CONCLUSIONS: Preoperative imaging was associated with longer wait times to surgery, more aggressive surgery, surgery with a gynecologic oncologist and increased use of neoadjuvant and adjuvant treatment. In early-stage disease there was no observed improvement in overall survival for patients with preoperative imaging. Further research on potential benefits of preoperative imaging in higher risk patients is required.

Remodeling of the Cortical Structural Connectome in Posttraumatic Stress Disorder: Results From the ENIGMA-PGC Posttraumatic Stress Disorder Consortium.

BACKGROUND: Posttraumatic stress disorder (PTSD) is accompanied by disrupted cortical neuroanatomy. We investigated alteration in covariance of structural networks associated with PTSD in regions that demonstrate the case-control differences in cortical thickness (CT) and surface area (SA). METHODS: Neuroimaging and clinical data were aggregated from 29 research sites in >1300 PTSD cases and >2000 trauma-exposed control subjects (ages 6.2-85.2 years) by the ENIGMA-PGC (Enhancing Neuro Imaging Genetics through Meta Analysis-Psychiatric Genomics Consortium) PTSD working group. Cortical regions in the network were rank ordered by the effect size of PTSD-related cortical differences in CT and SA. The top-n (n = 2-148) regions with the largest effect size for PTSD > non-PTSD formed hypertrophic networks, the largest effect size for PTSD < non-PTSD formed atrophic networks, and the smallest effect size of between-group differences formed stable networks. The mean structural covariance (SC) of a given n-region network was the average of all positive pairwise correlations and was compared with the mean SC of 5000 randomly generated n-region networks. RESULTS: Patients with PTSD, relative to non-PTSD control subjects, exhibited lower mean SC in CT-based and SA-based atrophic networks. Comorbid depression, sex, and age modulated covariance differences of PTSD-related structural networks. CONCLUSIONS: Covariance of structural networks based on CT and cortical SA are affected by PTSD and further modulated by comorbid depression, sex, and age. The SC networks that are perturbed in PTSD comport with converging evidence from resting-state functional connectivity networks and networks affected by inflammatory processes and stress hormones in PTSD.

National Healthcare Safety Network 2018 Baseline Neonatal Standardized Antimicrobial Administration Ratios.

BACKGROUND: The microbiologic etiologies, clinical manifestations, and antimicrobial treatment of neonatal infections differ substantially from infections in adult and pediatric patient populations. In 2019, the Centers for Disease Control and Prevention developed neonatal-specific (Standardized Antimicrobial Administration Ratios SAARs), a set of risk-adjusted antimicrobial use metrics that hospitals participating in the National Healthcare Safety Network's (NHSN's) antimicrobial use surveillance can use in their antibiotic stewardship programs (ASPs). METHODS: The Centers for Disease Control and Prevention, in collaboration with the Vermont Oxford Network, identified eligible patient care locations, defined SAAR agent categories, and implemented neonatal-specific NHSN Annual Hospital Survey questions to gather hospital-level data necessary for risk adjustment. SAAR predictive models were developed using 2018 data reported to NHSN from eligible neonatal units. RESULTS: The 2018 baseline neonatal SAAR models were developed for 7 SAAR antimicrobial agent categories using data reported from 324 neonatal units in 304 unique hospitals. Final models were used to calculate predicted antimicrobial days, the SAAR denominator, for level II neonatal special care nurseries and level II/III, III, and IV NICUs. CONCLUSIONS: NHSN's initial set of neonatal SAARs provides a way for hospital ASPs to assess whether antimicrobial agents in their facility are used at significantly higher or lower rates compared with a national baseline or whether an individual SAAR value is above or below a specific percentile on a given SAAR distribution, which can prompt investigations into prescribing practices and inform ASP interventions.

Association between prevalence of laboratory-identified Clostridioides difficile infection (CDI) and antibiotic treatment for CDI in US acute-care hospitals, 2019.

OBJECTIVE: To evaluate hospital-level variation in using first-line antibiotics for Clostridioides difficile infection (CDI) based on the burden of laboratory-identified (LabID) CDI. METHODS: Using data on hospital-level LabID CDI events and antimicrobial use (AU) for CDI (oral/rectal vancomycin or fidaxomicin) submitted to the National Healthcare Safety Network in 2019, we assessed the association between hospital-level CDI prevalence (per 100 patient admissions) and rate of CDI AU (days of therapy per 1,000 days present) to generate a predicted value of AU based on CDI prevalence and CDI test type using negative binomial regression. The ratio of the observed to predicted AU was then used to identify hospitals with extreme discordance between CDI prevalence and CDI AU, defined as hospitals with a ratio outside of the intervigintile range. RESULTS: Among 963 acute-care hospitals, rate of CDI prevalence demonstrated a positive dose-response relationship with rate of CDI AU. Compared with hospitals without extreme discordance (n = 902), hospitals with lower-than-expected CDI AU (n = 31) had, on average, fewer beds (median, 106 vs 208), shorter length of stay (median, 3.8 vs 4.2 days), and higher proportion of undergraduate or nonteaching medical school affiliation (48% vs 39%). Hospitals with higher-than-expected CDI AU (n = 30) were similar overall to hospitals without extreme discordance. CONCLUSIONS: The prevalence rate of LabID CDI had a significant dose-response association with first-line antibiotics for treating CDI. We identified hospitals with extreme discordance between CDI prevalence and CDI AU, highlighting potential opportunities for data validation and improvements in diagnostic and treatment practices for CDI.

Impact of coronavirus disease 2019 (COVID-19) on US Hospitals and Patients, April-July 2020.

OBJECTIVE: The rapid spread of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) throughout key regions of the United States in early 2020 placed a premium on timely, national surveillance of hospital patient censuses. To meet that need, the Centers for Disease Control and Prevention's National Healthcare Safety Network (NHSN), the nation's largest hospital surveillance system, launched a module for collecting hospital coronavirus disease 2019 (COVID-19) data. We present time-series estimates of the critical hospital capacity indicators from April 1 to July 14, 2020. DESIGN: From March 27 to July 14, 2020, the NHSN collected daily data on hospital bed occupancy, number of hospitalized patients with COVID-19, and the availability and/or use of mechanical ventilators. Time series were constructed using multiple imputation and survey weighting to allow near-real-time daily national and state estimates to be computed. RESULTS: During the pandemic's April peak in the United States, among an estimated 431,000 total inpatients, 84,000 (19%) had COVID-19. Although the number of inpatients with COVID-19 decreased from April to July, the proportion of occupied inpatient beds increased steadily. COVID-19 hospitalizations increased from mid-June in the South and Southwest regions after stay-at-home restrictions were eased. The proportion of inpatients with COVID-19 on ventilators decreased from April to July. CONCLUSIONS: The NHSN hospital capacity estimates served as important, near-real-time indicators of the pandemic's magnitude, spread, and impact, providing quantitative guidance for the public health response. Use of the estimates detected the rise of hospitalizations in specific geographic regions in June after they declined from a peak in April. Patient outcomes appeared to improve from early April to mid-July.

Reimagining the Introductory Math Curriculum for Life Sciences Students.

Calculus is typically one of the first college courses encountered by science, technology, engineering, and mathematics (STEM) majors. Calculus often presents major challenges affecting STEM student persistence, particularly for students from groups historically underrepresented in STEM. For life sciences majors, calculus courses may not offer content that is relevant to biological systems or connect with students' interests in biology. We developed a transformative approach to teaching college-level math, using a dynamical systems perspective that focuses first on demonstrating why students need math to understand living systems, followed by providing quantitative and computational skills, including concepts from calculus, that students need to build and analyze mathematical models representing these systems. We found that students who complete these new math courses perform better in subsequent science courses than their counterparts who take traditional calculus courses. We also provide evidence that the new math curriculum positively impacts students' academic performance, with data that show narrowing of the achievement gap, based on students' math grades, between student subgroups in the new math courses. Moreover, our results indicate that students' interest in the concepts and skills critical to the quantitative preparation of 21st-century life sciences majors increases after completing the new contextualized math curriculum.

Association between end-of-life cancer care and immigrant status: a retrospective cohort study in Ontario, Canada.

OBJECTIVE: To compare recent immigrants and long-term residents in Ontario, Canada, on established health service quality indicators of end-of-life cancer care. DESIGN: Retrospective, population-based cohort study of cancer decedents between 2004 and 2015. SETTING: Ontario, Canada. PARTICIPANTS: We grouped 13 085 immigrants who arrived in Ontario in 1985 or later into eight major ethnic groups based on birth country, mother tongue and surname, and compared them to 229 471 long-term residents who were ≥18 years at the time of death. PRIMARY AND SECONDARY OUTCOME MEASURES: Aggressive care, defined as a composite of ≥2 emergency department visits, ≥2 new hospitalisations or an intensive care unit admission within 30 days of death; and supportive care, defined as a physician house call within 2 weeks, or palliative nursing or personal support worker home visit within 6 months of death. Multivariable logistic regression was used to examine the association between immigration status and the odds of each main outcome. RESULTS: Compared with long-term residents, immigrants overall and by ethnic group had higher rates of aggressive care (13.7% vs 17.5%, respectively; p<0.001). Among immigrants, Southeast Asians had the highest use while White-Eastern and Western Europeans had the lowest. Supportive care use was similar between long-term residents and immigrants (50.0% vs 50.5%, respectively; p=0.36), though lower among Southeast Asians (46.6%) and higher among White-Western Europeans (55.6%). After adjusting for sociodemographic characteristics and comorbidities, immigrants remained more likely than long-term residents to receive aggressive care (OR: 1.15, 95% CI 1.09 to 1.21), yet were less likely to receive supportive care (OR: 0.95, 95% CI 0.91 to 0.98). CONCLUSIONS: Among cancer decedents in Ontario, immigrants are more likely to use aggressive healthcare services at the end of life than long-term residents, while supportive care varies by ethnicity. Contributors to variation in end-of-life care require further study.

The use of imaging in endometrial cancer prior to potential surgery: Are guidelines being followed?

OBJECTIVES: Clinical practice guidelines recommend against routine preoperative axial imaging studies (CT/MRI) for endometrial cancer, except for cases of locally advanced disease or aggressive histologies. This study utilized population-based data to evaluate the use of preoperative imaging and factors associated with its use. METHODS: A population-based cohort of women diagnosed with endometrial cancer from 2006 to 2016 were identified from the Ontario Cancer Registry in Ontario, Canada. Patients were excluded if they had: hysterectomy prior to the date of diagnosis, non-epithelial histology or a prior cancer diagnosis within 5 years. Preoperative imaging (CT or MRI) rates were calculated over time. Predictive factors for preoperative imaging use were determined using multi-variable regression analysis. RESULTS: 17,718 cases were eligible for analysis. From 2006 to 2016, the proportion of patients receiving preoperative imaging increased from 22.2% to 39.3%. In a subgroup of patients with low-risk disease (stage 1, endometrioid adenocarcinoma), imaging increased from 16.3% to 29.5%. Multivariate analysis showed an association between preoperative imaging and advanced stage, advanced grade, non-endometrioid morphology, surgery with a gynecologic oncologist, surgery at a teaching hospital and a later year of diagnosis. From 2006 to 2016, the yearly incidence of endometrial cancer increased from 22.3/100,000 to 36.1/100,000, representing a mean annual increase of 3.6% per year. CONCLUSIONS: Endometrial cancer incidence and the use of preoperative imaging are increasing. Factors most associated with preoperative imaging are high-risk features. However, preoperative imaging is still being performed in low-risk patients, indicating non-adherence to guidelines, which has implications for constrained healthcare resources.

Assessment of the Appropriateness of Antimicrobial Use in US Hospitals.

Importance: Hospital antimicrobial consumption data are widely available; however, large-scale assessments of the quality of antimicrobial use in US hospitals are limited. Objective: To evaluate the appropriateness of antimicrobial use for hospitalized patients treated for community-acquired pneumonia (CAP) or urinary tract infection (UTI) present at admission or for patients who had received fluoroquinolone or intravenous vancomycin treatment. Design, Setting, and Participants: This cross-sectional study included data from a prevalence survey of hospitalized patients in 10 Emerging Infections Program sites. Random samples of inpatients on hospital survey dates from May 1 to September 30, 2015, were identified. Medical record data were collected for eligible patients with 1 or more of 4 treatment events (CAP, UTI, fluoroquinolone treatment, or vancomycin treatment), which were selected on the basis of common infection types reported and antimicrobials given to patients in the prevalence survey. Data were analyzed from August 1, 2017, to May 31, 2020. Exposure: Antimicrobial treatment for CAP or UTI or with fluoroquinolones or vancomycin. Main Outcomes and Measures: The percentage of antimicrobial use that was supported by medical record data (including infection signs and symptoms, microbiology test results, and antimicrobial treatment duration) or for which some aspect of use was unsupported. Unsupported antimicrobial use was defined as (1) use of antimicrobials to which the pathogen was not susceptible, use in the absence of documented infection signs or symptoms, or use without supporting microbiologic data; (2) use of antimicrobials that deviated from recommended guidelines; or (3) use that exceeded the recommended duration. Results: Of 12 299 patients, 1566 patients (12.7%) in 192 hospitals were included; the median age was 67 years (interquartile range, 53-79 years), and 864 (55.2%) were female. A total of 219 patients (14.0%) were included in the CAP analysis, 452 (28.9%) in the UTI analysis, 550 (35.1%) in the fluoroquinolone analysis, and 403 (25.7%) in the vancomycin analysis; 58 patients (3.7%) were included in both fluoroquinolone and vancomycin analyses. Overall, treatment was unsupported for 876 of 1566 patients (55.9%; 95% CI, 53.5%-58.4%): 110 of 403 (27.3%) who received vancomycin, 256 of 550 (46.6%) who received fluoroquinolones, 347 of 452 (76.8%) with a diagnosis of UTI, and 174 of 219 (79.5%) with a diagnosis of CAP. Among patients with unsupported treatment, common reasons included excessive duration (103 of 174 patients with CAP [59.2%]) and lack of documented infection signs or symptoms (174 of 347 patients with UTI [50.1%]). Conclusions and Relevance: The findings suggest that standardized assessments of hospital antimicrobial prescribing quality can be used to estimate the appropriateness of antimicrobial use in large groups of hospitals. These assessments, performed over time, may inform evaluations of the effects of antimicrobial stewardship initiatives nationally.

Antimicrobial Use in US Hospitals: Comparison of Results From Emerging Infections Program Prevalence Surveys, 2015 and 2011.

BACKGROUND: In the 2011 US hospital prevalence survey of healthcare-associated infections and antimicrobial use 50% of patients received antimicrobial medications on the survey date or day before. More hospitals have since established antimicrobial stewardship programs. We repeated the survey in 2015 to determine antimicrobial use prevalence and describe changes since 2011. METHODS: The Centers for Disease Control and Prevention's Emerging Infections Program sites in 10 states each recruited ≤25 general and women's and children's hospitals. Hospitals selected a survey date from May-September 2015. Medical records for a random patient sample on the survey date were reviewed to collect data on antimicrobial medications administered on the survey date or day before. Percentages of patients on antimicrobial medications were compared; multivariable log-binomial regression modeling was used to evaluate factors associated with antimicrobial use. RESULTS: Of 12 299 patients in 199 hospitals, 6084 (49.5%; 95% CI, 48.6-50.4%) received antimicrobials. Among 148 hospitals in both surveys, overall antimicrobial use prevalence was similar in 2011 and 2015, although the percentage of neonatal critical care patients on antimicrobials was lower in 2015 (22.8% vs 32.0% [2011]; P = .006). Fluoroquinolone use was lower in 2015 (10.1% of patients vs 11.9% [2011]; P < .001). Third- or fourth-generation cephalosporin use was higher (12.2% vs 10.7% [2011]; P = .002), as was carbapenem use (3.7% vs 2.7% [2011]; P < .001). CONCLUSIONS: Overall hospital antimicrobial use prevalence was not different in 2011 and 2015; however, differences observed in selected patient or antimicrobial groups may provide evidence of stewardship impact.