Diagnostic Discordance, Uncertainty, and Treatment Ambiguity in Community-Acquired Pneumonia : A National Cohort Study of 115 U.S. Veterans Affairs Hospitals.

BACKGROUND: Evidence-based practice in community-acquired pneumonia often assumes an accurate initial diagnosis. OBJECTIVE: To examine the evolution of pneumonia diagnoses among patients hospitalized from the emergency department (ED). DESIGN: Retrospective nationwide cohort. SETTING: 118 U.S. Veterans Affairs medical centers. PATIENTS: Aged 18 years or older and hospitalized from the ED between 1 January 2015 and 31 January 2022. MEASUREMENTS: Discordances between initial pneumonia diagnosis, discharge diagnosis, and radiographic diagnosis identified by natural language processing of clinician text, diagnostic coding, and antimicrobial treatment. Expressions of uncertainty in clinical notes, patient illness severity, treatments, and outcomes were compared. RESULTS: Among 2 383 899 hospitalizations, 13.3% received an initial or discharge diagnosis and treatment of pneumonia: 9.1% received an initial diagnosis and 10.0% received a discharge diagnosis. Discordances between initial and discharge occurred in 57%. Among patients discharged with a pneumonia diagnosis and positive initial chest image, 33% lacked an initial diagnosis. Among patients diagnosed initially, 36% lacked a discharge diagnosis and 21% lacked positive initial chest imaging. Uncertainty was frequently expressed in clinical notes (58% in ED; 48% at discharge); 27% received diuretics, 36% received corticosteroids, and 10% received antibiotics, corticosteroids, and diuretics within 24 hours. Patients with discordant diagnoses had greater uncertainty and received more additional treatments, but only patients lacking an initial pneumonia diagnosis had higher 30-day mortality than concordant patients (14.4% [95% CI, 14.1% to 14.7%] vs. 10.6% [CI, 10.4% to 10.7%]). Patients with diagnostic discordance were more likely to present to high-complexity facilities with high ED patient load and inpatient census. LIMITATION: Retrospective analysis; did not examine causal relationships. CONCLUSION: More than half of all patients hospitalized and treated for pneumonia had discordant diagnoses from initial presentation to discharge. Treatments for other diagnoses and expressions of uncertainty were common. These findings highlight the need to recognize diagnostic uncertainty and treatment ambiguity in research and practice of pneumonia-related care. PRIMARY FUNDING SOURCE: The Gordon and Betty Moore Foundation.

Disparities and Medical Expenditure Implications in Pediatric Tele-Mental Health Services During the COVID-19 Pandemic in Mississippi.

Tele-mental health (TMH) services, including both mental and behavioral healthcare (MBH) services, emerged as a cornerstone in delivering pediatric mental healthcare during the coronavirus disease 2019 (COVID-19) pandemic, yet their utilization and effects on healthcare resource utilization (HCRU) and medical expenditures remain unclear. To bridge the gap, this study aims to investigate the association between TMH utilization and sociodemographic factors and assess its associated HCRU and medical expenditures within a pediatric population in Mississippi. Studying 1,972 insured pediatric patients who accessed outpatient MBH services at the study institution between January 2020 and June 2023, age, race, insurance type, rural residency, and household income were identified as key determinants of TMH utilization. Adjusting for sociodemographics, TMH utilization was associated with 122% more MBH-associated outpatient visits and 36% higher related medical expenditures, but 27% less overall medical expenditures. This study reveals sociodemographic disparities in pediatric TMH utilization, highlights its role in augmenting outpatient mental healthcare access, and shows its potential for cost savings. Future efforts should aim at fostering more digitally inclusive, equitable, and affordable pediatric mental healthcare services.

Post-infectious Pulmonary Complications: Establishing Research Priorities to Advance the Field. An Official American Thoracic Society Workshop Report.

Continued improvements in the treatment of pulmonary infections have paradoxically resulted in a growing challenge of individuals with post-infectious pulmonary complications (PIPCs). PIPCs have been long recognized after tuberculosis but recent experiences, such as the SARS-CoV-2 pandemic, have underscored the importance of PIPCs following other lower respiratory tract infections. Independent of the causative pathogen, most available studies of pulmonary infections focus on short-term outcomes rather than long-term morbidity among survivors. In this document, we establish a conceptual scope for PIPCs with discussion of globally significant pulmonary pathogens and an examination of how these pathogens can damage different components of the lung, resulting in a spectrum of PIPCs. We also review potential mechanisms for the transition from acute infection to PIPC, including the interplay between pathogen-mediated injury and aberrant host responses, which together result in PIPCs. Finally, we identify cross-cutting research priorities for the field to facilitate future studies to establish the incidence of PIPCs, define common mechanisms, identify therapeutic strategies, and ultimately reduce the burden of morbidity in survivors of pulmonary infections.

Tele-Mental Health Service: Unveiling the Disparity and Impact on Healthcare Access and Expenditures during the COVID-19 Pandemic in Mississippi.

During the COVID-19 pandemic, tele-mental health (TMH) was a viable approach for providing accessible mental and behavioral health (MBH) services. This study examines the sociodemographic disparities in TMH utilization and its effects on healthcare resource utilization (HCRU) and medical expenditures in Mississippi. Utilizing a cohort of 6787 insured adult patients at the University of Mississippi Medical Center and its affiliated sites between January 2020 and June 2023, including 3065 who accessed TMH services, we observed sociodemographic disparities between TMH and non-TMH cohorts. The TMH cohort was more likely to be younger, female, White/Caucasian, using payment methods other than Medicare, Medicaid, or commercial insurers, residing in rural areas, and with higher household income compared to the non-TMH cohort. Adjusting for sociodemographic factors, TMH utilization was associated with a 190% increase in MBH-related outpatient visits, a 17% increase in MBH-related medical expenditures, and a 12% decrease in all-cause medical expenditures (all p < 0.001). Among rural residents, TMH utilization was associated with a 205% increase in MBH-related outpatient visits and a 19% decrease in all-cause medical expenditures (both p < 0.001). This study underscores the importance of addressing sociodemographic disparities in TMH services to promote equitable healthcare access while reducing overall medical expenditures.

A MYCN-driven de-differentiation profile identifies a subgroup of aggressive retinoblastoma.

Retinoblastoma are childhood eye tumors arising from retinal precursor cells. Two distinct retinoblastoma subtypes with different clinical behavior have been described based on gene expression and methylation profiling. Using consensus clustering of DNA methylation analysis from 61 retinoblastomas, we identify a MYCN-driven cluster of subtype 2 retinoblastomas characterized by DNA hypomethylation and high expression of genes involved in protein synthesis. Subtype 2 retinoblastomas outside the MYCN-driven cluster are characterized by high expression of genes from mesodermal development, including NKX2-5. Knockdown of MYCN expression in retinoblastoma cell models causes growth arrest and reactivates a subtype 1-specific photoreceptor signature. These molecular changes suggest that removing the driving force of MYCN oncogenic activity rescues molecular circuitry driving subtype 1 biology. The MYCN-RB gene signature generated from the cell models better identifies MYCN-driven retinoblastoma than MYCN amplification and can identify cases that may benefit from MYCN-targeted therapy. MYCN drives tumor progression in a molecularly defined retinoblastoma subgroup, and inhibiting MYCN activity could restore a more differentiated and less aggressive tumor biology.

Incorporating social determinants of health into transmission modeling of COVID-19 vaccine in the US: a scoping review.

During COVID-19 in the US, social determinants of health (SDH) have driven health disparities. However, the use of SDH in COVID-19 vaccine modeling is unclear. This review aimed to summarize the current landscape of incorporating SDH into COVID-19 vaccine transmission modeling in the US. Medline and Embase were searched up to October 2022. We included studies that used transmission modeling to assess the effects of COVID-19 vaccine strategies in the US. Studies' characteristics, factors incorporated into models, and approaches to incorporate these factors were extracted. Ninety-two studies were included. Of these, 11 studies incorporated SDH factors (alone or combined with demographic factors). Various sets of SDH factors were integrated, with occupation being the most common (8 studies), followed by geographical location (5 studies). The results show that few studies incorporate SDHs into their models, highlighting the need for research on SDH impact and approaches to incorporating SDH into modeling. Funding: This research was funded by the Centers for Disease Control and Prevention (CDC).

Automating detection of diagnostic error of infectious diseases using machine learning.

Diagnostic error, a cause of substantial morbidity and mortality, is largely discovered and evaluated through self-report and manual review, which is costly and not suitable to real-time intervention. Opportunities exist to leverage electronic health record data for automated detection of potential misdiagnosis, executed at scale and generalized across diseases. We propose a novel automated approach to identifying diagnostic divergence considering both diagnosis and risk of mortality. Our objective was to identify cases of emergency department infectious disease misdiagnoses by measuring the deviation between predicted diagnosis and documented diagnosis, weighted by mortality. Two machine learning models were trained for prediction of infectious disease and mortality using the first 24h of data. Charts were manually reviewed by clinicians to determine whether there could have been a more correct or timely diagnosis. The proposed approach was validated against manual reviews and compared using the Spearman rank correlation. We analyzed 6.5 million ED visits and over 700 million associated clinical features from over one hundred emergency departments. The testing set performances of the infectious disease (Macro F1 = 86.7, AUROC 90.6 to 94.7) and mortality model (Macro F1 = 97.6, AUROC 89.1 to 89.1) were in expected ranges. Human reviews and the proposed automated metric demonstrated positive correlations ranging from 0.231 to 0.358. The proposed approach for diagnostic deviation shows promise as a potential tool for clinicians to find diagnostic errors. Given the vast number of clinical features used in this analysis, further improvements likely need to either take greater account of data structure (what occurs before when) or involve natural language processing. Further work is needed to explain the potential reasons for divergence and to refine and validate the approach for implementation in real-world settings.

Pneumonia diagnosis performance in the emergency department: a mixed-methods study about clinicians' experiences and exploration of individual differences and response to diagnostic performance feedback.

OBJECTIVES: We sought to (1) characterize the process of diagnosing pneumonia in an emergency department (ED) and (2) examine clinician reactions to a clinician-facing diagnostic discordance feedback tool. MATERIALS AND METHODS: We designed a diagnostic feedback tool, using electronic health record data from ED clinicians' patients to establish concordance or discordance between ED diagnosis, radiology reports, and hospital discharge diagnosis for pneumonia. We conducted semistructured interviews with 11 ED clinicians about pneumonia diagnosis and reactions to the feedback tool. We administered surveys measuring individual differences in mindset beliefs, comfort with feedback, and feedback tool usability. We qualitatively analyzed interview transcripts and descriptively analyzed survey data. RESULTS: Thematic results revealed: (1) the diagnostic process for pneumonia in the ED is characterized by diagnostic uncertainty and may be secondary to goals to treat and dispose the patient; (2) clinician diagnostic self-evaluation is a fragmented, inconsistent process of case review and follow-up that a feedback tool could fill; (3) the feedback tool was described favorably, with task and normative feedback harnessing clinician values of high-quality patient care and personal excellence; and (4) strong reactions to diagnostic feedback varied from implicit trust to profound skepticism about the validity of the concordance metric. Survey results suggested a relationship between clinicians' individual differences in learning and failure beliefs, feedback experience, and usability ratings. DISCUSSION AND CONCLUSION: Clinicians value feedback on pneumonia diagnoses. Our results highlight the importance of feedback about diagnostic performance and suggest directions for considering individual differences in feedback tool design and implementation.

Community Health Work and Social Work Collaboration: Integration in Health Care and Public Health Settings: A Conceptual Framework.

Community health worker (CHW) and social worker (SW) collaboration is crucial to illness prevention and intervention, yet systems often engage the 2 workforces in silos and miss opportunities for cross-sector alignment. In 2021, a national workgroup of over 2 dozen CHWs, SWs, and public health experts convened to improve CHW/SW collaboration and integration across the United States. The workgroup developed a conceptual framework that describes structural, systemic, and organizational factors that influence CHW/SW collaboration. Best practices include standardized training, delineated roles and scopes of practice, clear workflows, regular communication, a shared system for documentation, and ongoing support or supervision.

Rapid Market Screening to assess lead concentrations in consumer products across 25 low- and middle-income countries.

Lead exposure can have serious consequences for health and development. The neurological and behavioral effects of lead are considered irreversible. Young children are particularly vulnerable to lead poisoning. In 2020, Pure Earth and UNICEF estimated that one in three children had elevated blood lead levels above 5 µg/dL. The sources of lead exposure vary around the world and can range from household products, such as spices or foodware, to environmental pollution from nearby industries. The aim of this study was to analyze common products from markets in low- and middle-income countries (LMICs) for their lead content to determine whether they are plausible sources of exposure. In 25 LMICs, the research teams systematically collected consumer products (metal foodware, ceramics, cosmetics, paints, toys, spices and other foods). The items were analyzed on site for detectable lead above 2 ppm using an X-ray fluorescence analyzer. For quality control purposes, a subset of the samples was analyzed in the USA using inductively coupled plasma mass spectrometry. The lead concentrations of the individual product types were compared with established regulatory thresholds. Out of 5007 analyzed products, threshold values (TV) were surpassed in 51% for metal foodware (TV 100 ppm), 45% for ceramics (TV 100 ppm), and 41% for paints (TV 90 ppm). Sources of exposure in LMICs can be diverse, and consumers in LMICs lack adequate protection from preventable sources of lead exposure. Rapid Market Screening is an innovative, simple, and useful tool to identify risky products that could be sources of lead exposure.

Diagnosis and Treatment of Pneumonia in Urgent Care Clinics: Opportunities for Improving Care.

Background: Community-acquired pneumonia is a well-studied condition; yet, in the urgent care setting, patient characteristics and adherence to guideline-recommended care are poorly described. Within Intermountain Health, a nonprofit integrated US health care system based in Utah, more patients present to urgent care clinics (UCCs) than emergency departments (EDs) for pneumonia care. Methods: We performed a retrospective cohort study 1 January 2019 through 31 December 2020 in 28 UCCs within Utah. We extracted electronic health record data for patients aged ≥12 years with ICD-10 pneumonia diagnoses entered by the bedside clinician, excluding patients with preceding pneumonia within 30 days or missing vital signs. We compared UCC patients with radiographic pneumonia (n = 4689), without radiographic pneumonia (n = 1053), without chest imaging (n = 1472), and matched controls with acute cough/bronchitis (n = 15 972). Additional outcomes were 30-day mortality and the proportion of patients with ED visits or hospital admission within 7 days after the index encounter. Results: UCC patients diagnosed with pneumonia and possible/likely radiographic pneumonia by radiologist report had a mean age of 40 years and 52% were female. Almost all patients with pneumonia (93%) were treated with antibiotics, including those without radiographic confirmation. Hospital admissions and ED visits within 7 days were more common in patients with radiographic pneumonia vs patients with "unlikely" radiographs (6% vs 2% and 10% vs 6%, respectively). Observed 30-day all-cause mortality was low (0.26%). Patients diagnosed without chest imaging presented similarly to matched patients with cough/acute bronchitis. Most patients admitted to the hospital the same day after the UCC visit (84%) had an interim ED encounter. Pneumonia severity scores (pneumonia severity index, electronic CURB-65, and shock index) overestimated patient need for hospitalization. Conclusions: Most UCC patients with pneumonia were successfully treated as outpatients. Opportunities to improve care include clinical decision support for diagnosing pneumonia with radiographic confirmation and development of pneumonia severity scores tailored to the UCC.

A Linguistic Analysis Examining the Impact of COVID-19 on Pneumonia Diagnosis and Disease Models.

Written clinical language embodies and reflects the clinician's mental models of disease. Prior to the COVID-19 pandemic, pneumonia was shifting away from concern for healthcare-associated pneumonia and toward recognition of heterogeneity of pathogens and host response. How these models are reflected in clinical language or whether they were impacted by the pandemic has not been studied. We aimed to assess changes in the language used to describe pneumonia following the COVID-19 pandemic.

Multi-omic and functional analysis for classification and treatment of sarcomas with FUS-TFCP2 or EWSR1-TFCP2 fusions.

Linking clinical multi-omics with mechanistic studies may improve the understanding of rare cancers. We leverage two precision oncology programs to investigate rhabdomyosarcoma with FUS/EWSR1-TFCP2 fusions, an orphan malignancy without effective therapies. All tumors exhibit outlier ALK expression, partly accompanied by intragenic deletions and aberrant splicing resulting in ALK variants that are oncogenic and sensitive to ALK inhibitors. Additionally, recurrent CKDN2A/MTAP co-deletions provide a rationale for PRMT5-targeted therapies. Functional studies show that FUS-TFCP2 blocks myogenic differentiation, induces transcription of ALK and truncated TERT, and inhibits DNA repair. Unlike other fusion-driven sarcomas, TFCP2-rearranged tumors exhibit genomic instability and signs of defective homologous recombination. DNA methylation profiling demonstrates a close relationship with undifferentiated sarcomas. In two patients, sarcoma was preceded by benign lesions carrying FUS-TFCP2, indicating stepwise sarcomagenesis. This study illustrates the potential of linking precision oncology with preclinical research to gain insight into the classification, pathogenesis, and therapeutic vulnerabilities of rare cancers.

Expressive Arts Interventions to Improve Psychosocial Well-Being in Caregivers: A Systematic Review.

CONTEXT: Over 43 million caregivers provide care and support in the United States. Increased stress and burden may contribute to poor psychosocial well-being. Recently, there has been an emergence of art-based interventions to improve well-being among care receivers and caregivers. A synthesis of this literature evaluating expressive arts interventions (EAIs) with caregivers is needed. OBJECTIVES: Identify the nature and impact of EAIs for caregivers and outline directions for future research. METHODS: Systematic searches were conducted in PubMed/MEDLINE, CINAHL, PsychINFO, and Web of Science for relevant studies between 2001 and 2022. Inclusion criteria included EAI addressing psychosocial well-being of caregivers, quantitative and mixed methods studies, and written in English. RESULTS: Twenty-seven studies were included (1359 participants). There was a diverse global representation of countries (n = 14). Twelve studies were randomized controlled trials. The majority (n = 11) were conducted with dementia/alzheimers caregivers and 41% (n = 11) were delivered to the caregiver/receiver dyad. Fifty-nine percent of the EAIs were music-based, 22% were visual arts, and 10% were writing. Intervention length varied from a single one-hour session to biweekly for 10-months; eight lasted two-weeks. Overall, stress improved in 80% of the studies, anxiety in 69%, caregiver burden in 57%, and depressive symptoms in 31%. CONCLUSION: Caregivers are essential to the care of people with medically complex and life-limiting conditions. EAIs hold the potential to improve psychosocial outcomes for caregivers, are used globally, and can be culturally tailored. Future research should examine intervention duration and intensity, measures to address additional dimensions of psychsocial well-being, and implementation in additional caregiver populations.

ICU Utilization After Implementation of Minor Severe Pneumonia Criteria in Real-Time Electronic Clinical Decision Support.

OBJECTIVES: To determine if the implementation of automated clinical decision support (CDS) with embedded minor severe community-acquired pneumonia (sCAP) criteria was associated with improved ICU utilization among emergency department (ED) patients with pneumonia who did not require vasopressors or positive pressure ventilation at admission. DESIGN: Planned secondary analysis of a stepped-wedge, cluster-controlled CDS implementation trial. SETTING: Sixteen hospitals in six geographic clusters from Intermountain Health; a large, integrated, nonprofit health system in Utah and Idaho. PATIENTS: Adults admitted to the hospital from the ED with pneumonia identified by: 1) discharge International Classification of Diseases , 10th Revision codes for pneumonia or sepsis/respiratory failure and 2) ED chest imaging consistent with pneumonia, who did not require vasopressors or positive pressure ventilation at admission. INTERVENTIONS: After implementation, patients were exposed to automated, open-loop, comprehensive CDS that aided disposition decision (ward vs. ICU), based on objective severity scores (sCAP). MEASUREMENTS AND MAIN RESULTS: The analysis included 2747 patients, 1814 before and 933 after implementation. The median age was 71, median Elixhauser index was 17, 48% were female, and 95% were Caucasian. A mixed-effects regression model with cluster as the random effect estimated that implementation of CDS utilizing sCAP increased 30-day ICU-free days by 1.04 days (95% CI, 0.48-1.59; p < 0.001). Among secondary outcomes, the odds of being admitted to the ward, transferring to the ICU within 72 hours, and receiving a critical therapy decreased by 57% (odds ratio [OR], 0.43; 95% CI, 0.26-0.68; p < 0.001) post-implementation; mortality within 72 hours of admission was unchanged (OR, 1.08; 95% CI, 0.56-2.01; p = 0.82) while 30-day all-cause mortality was lower post-implementation (OR, 0.71; 95% CI, 0.52-0.96; p = 0.03). CONCLUSIONS: Implementation of electronic CDS using minor sCAP criteria to guide disposition of patients with pneumonia from the ED was associated with safe reduction in ICU utilization.

Social workers are key to addressing social determinants of health in integrated care settings.

Social workers play an important role in assessing social determinants of health (SDH) and providing behavioral health services in integrated care settings. Evidence suggests that integrated care interventions improve quality of life and other patient outcomes. However, the ambiguous role of social workers on the interdisciplinary team, the lack of protocol in SDH screening and intervention, and restrictions due to healthcare reimbursement limit social workers' ability to intervene. Future directions include standardizing integrated care models, evaluating integrated care's efficacy to address SDH, incorporating SDH into interprofessional training including role clarification and reimbursing for SDH assessment and intervention.

Sociodemographic Correlates of Low Health Literacy Skills Among Cancer Survivors: National Findings From BRFSS 2016.

PURPOSE: This study aimed to explore associations of sociodemographic factors with difficulties in three health literacy (HL) skills and the severity of low HL skills. DESIGN: Cross-sectional secondary data analysis. Subjects: Data came from 17,834 adults who responded to the HL module with a response rate of 47% in the 2016 Behavioral Risk Factor Surveillance System. MEASURES: Independent variables included sex, age, race/ethnicity, education, employment and income. Dependent variables are three HL skills: obtaining, understanding oral, and understanding written health information. ANALYSIS: We conducted weighted Chi-square tests and multinominal logistic regressions. RESULTS: Cancer survivors younger than 65 (aged 18-39: AOR = 4.46, P < .001; aged 40-64: AOR = 2.29, P < .001), Hispanic (AOR = 2.17, CI = 1.61-2.50, P < .01) had higher odds of difficulty obtaining health information. Female cancer survivors had lower odds of difficulty comprehending oral (AOR = .69, CI = .55-.87, P < .01) and written (AOR = .58, CI = .46-.74, P < .001) information. The relative risk ratio of having difficulties in three HL tasks was higher for those who were younger than 65 (aged 18-39: RRR = 10.18, CI = 2.41-4.3, P < .01; aged 40-64: RRR = 4.01, CI = 2.09-7.69, P < .001), Hispanic (RRR = 3.24, CI = 1.66-11.34, P < .01), unemployed (RRR = 6.1, CI = 2.88-12.76, P < .001), education levels lower than some college (some high school: RRR = 4.34, P < .01; high school: RRR = 2.62, P < .05) and household income under $25,000 (RRR = 6.99, CI = 2.8-17.5, P < .001). CONCLUSION: Intervention and communication materials need to be tailored for patients with different HL skills considering age, gender, socioeconomic status and cultural backgrounds.

Disparities in COVID-19 related outcomes in the United States by race and ethnicity pre-vaccination era: an umbrella review of meta-analyses.

Background: Meta-analyses have investigated associations between race and ethnicity and COVID-19 outcomes. However, there is uncertainty about these associations' existence, magnitude, and level of evidence. We, therefore, aimed to synthesize, quantify, and grade the strength of evidence of race and ethnicity and COVID-19 outcomes in the US. Methods: In this umbrella review, we searched four databases (Pubmed, Embase, the Cochrane Database of Systematic Reviews, and Epistemonikos) from database inception to April 2022. The methodological quality of each meta-analysis was assessed using the Assessment of Multiple Systematic Reviews, version 2 (AMSTAR-2). The strength of evidence of the associations between race and ethnicity with outcomes was ranked according to established criteria as convincing, highly suggestive, suggestive, weak, or non-significant. The study protocol was registered with PROSPERO, CRD42022336805. Results: Of 880 records screened, we selected seven meta-analyses for evidence synthesis, with 42 associations examined. Overall, 10 of 42 associations were statistically significant (p ≤ 0.05). Two associations were highly suggestive, two were suggestive, and two were weak, whereas the remaining 32 associations were non-significant. The risk of COVID-19 infection was higher in Black individuals compared to White individuals (risk ratio, 2.08, 95% Confidence Interval (CI), 1.60-2.71), which was supported by highly suggestive evidence; with the conservative estimates from the sensitivity analyses, this association remained suggestive. Among those infected with COVID-19, Hispanic individuals had a higher risk of COVID-19 hospitalization than non-Hispanic White individuals (odds ratio, 2.08, 95% CI, 1.60-2.70) with highly suggestive evidence which remained after sensitivity analyses. Conclusion: Individuals of Black and Hispanic groups had a higher risk of COVID-19 infection and hospitalization compared to their White counterparts. These associations of race and ethnicity and COVID-19 outcomes existed more obviously in the pre-hospitalization stage. More consideration should be given in this stage for addressing health inequity.

Epigenetic aging in cows is accelerated by milk production.

DNA methylation has proven to be the most promising age-predictive biomarker in mammals resulting in the emergence of 'epigenetic clocks' that describe the relationship between methylation levels and age. Using Targeted bisulfite Sequencing, we evaluated blood DNA-methylation data from 96 domesticated cows (Bos Taurus) of which 88 were adults and 8 were calves. This allowed us to measure DNA methylation across three thousand regions in the genome that were conserved across mammals. The significant association of age with the changes in DNA methylation enabled us to construct an epigenetic clock that predicts the age of cows to within nine months. We also investigated whether factors exist that moderate the association between epigenetic age and actual age and found that milk production levels significantly increase the rate of epigenetic ageing, suggesting that the stress of excessive milk production might be accelerating epigenetic ageing in cows.