Racial and Ethnic Differences in Hospital Admissions of Emergency Department COVID-19 Patients.

BACKGROUND: Several studies have found that among patients testing positive for COVID-19 within a health care system, non-Hispanic Black and Hispanic patients are more likely than non-Hispanic White patients to be hospitalized. However, previous studies have looked at odds of being admitted using all positive tests in the system and not only those seeking care in the emergency department (ED). OBJECTIVE: This study examined racial/ethnic differences in COVID-19 hospitalizations and intensive care unit (ICU) admissions among patients seeking care for COVID-19 in the ED. RESEARCH DESIGN: Electronic health records (n=7549) were collected from COVID-19 confirmed patients that visited an ED of an urban health care system in the Chicago area between March 2020 and February 2021. RESULTS: After adjusting for possible confounders, White patients had 2.2 times the odds of being admitted to the hospital and 1.5 times the odds of being admitted to the ICU than Black patients. There were no observed differences between White and Hispanic patients. CONCLUSIONS: White patients were more likely than Black patients to be hospitalized after presenting to the ED with COVID-19 and more likely to be admitted directly to the ICU. This finding may be due to racial/ethnic differences in severity of disease upon ED presentation, racial and ethnic differences in access to COVID-19 primary care and/or implicit bias impacting clinical decision-making.

COVID-19 Among African Americans: An Action Plan for Mitigating Disparities.

As the COVID-19 pandemic has unfolded across the United States, troubling disparities in mortality have emerged between different racial groups, particularly African Americans and Whites. Media reports, a growing body of COVID-19-related literature, and long-standing knowledge of structural racism and its myriad effects on the African American community provide important lenses for understanding and addressing these disparities.However, troubling gaps in knowledge remain, as does a need to act. Using the best available evidence, we present risk- and place-based recommendations for how to effectively address these disparities in the areas of data collection, COVID-19 exposure and testing, health systems collaboration, human capital repurposing, and scarce resource allocation.Our recommendations are supported by an analysis of relevant bioethical principles and public health practices. Additionally, we provide information on the efforts of Chicago, Illinois' mayoral Racial Equity Rapid Response Team to reduce these disparities in a major urban US setting.

Treatment pathway analysis of newly diagnosed dementia patients in four electronic health record databases in Europe.

PURPOSE: Real-world studies to describe the use of first, second and third line therapies for the management and symptomatic treatment of dementia are lacking. This retrospective cohort study describes the first-, second- and third-line therapies used for the management and symptomatic treatment of dementia, and in particular Alzheimer's Disease. METHODS: Medical records of patients with newly diagnosed dementia between 1997 and 2017 were collected using four databases from the UK, Denmark, Italy and the Netherlands. RESULTS: We identified 191,933 newly diagnosed dementia patients in the four databases between 1997 and 2017 with 39,836 (IPCI (NL): 3281, HSD (IT): 1601, AUH (DK): 4474, THIN (UK): 30,480) fulfilling the inclusion criteria, and of these, 21,131 had received a specific diagnosis of Alzheimer's disease. The most common first line therapy initiated within a year (± 365 days) of diagnosis were Acetylcholinesterase inhibitors, namely rivastigmine in IPCI, donepezil in HSD and the THIN and the N-methyl-D-aspartate blocker memantine in AUH. CONCLUSION: We provide a real-world insight into the heterogeneous management and treatment pathways of newly diagnosed dementia patients and a subset of Alzheimer's Disease patients from across Europe.

Racial/ethnic minority segregation and low birth weight in five North American cities.

Comparisons of communities across cities are rare in social epidemiology. Our prior work exploring racial/ethnic segregation and the prevalence of low birth weight (LBW) in communities from two large urban cities showed a strong relationship in Chicago and a very weak relationship in Toronto. This study extends that work by examining the association between racial/ethnic minority segregation and LBW in total of 307 communities in five North American cities: Baltimore, Boston, Chicago, Philadelphia, and Toronto. We used Pearson correlation coefficients and OLS regression models to examine potential variability in the association between racial/ethnic minority segregation and LBW, controlling for community-level unemployment. In a combined model with community-level data from all cities, a 10% increase in minority composition is associated with a 0.7% increase in LBW. While racial/ethnic minority segregation and unemployment are not associated with LBW in Toronto, these social determinants have strong and significant associations with LBW across communities in the four US cities in the analysis. Subsequent models revealed opposite effects for percentage non-Hispanic Black and percentage Hispanic. Across communities in the US cities in this analysis, there is considerable similarity in the strength of the effect of racial/ethnic segregation on LBW. Future work should incorporate communities from additional cities, looking to identify community assets and public policies that allow some minority communities to thrive, while other minority communities suffer from a high prevalence of LBW. More work is also needed on the generalizability of these patterns to other health outcomes.

Risks and clinical predictors of cirrhosis and hepatocellular carcinoma diagnoses in adults with diagnosed NAFLD: real-world study of 18 million patients in four European cohorts.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a common condition that progresses in some patients to steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC). Here we used healthcare records of 18 million adults to estimate risk of acquiring advanced liver disease diagnoses in patients with NAFLD or NASH compared to individually matched controls. METHODS: Data were extracted from four European primary care databases representing the UK, Netherlands, Italy and Spain. Patients with a recorded diagnosis of NAFLD or NASH (NAFLD/NASH) were followed up for incident cirrhosis and HCC diagnoses. Each coded NAFLD/NASH patient was matched to up to 100 "non-NAFLD" patients by practice site, gender, age ± 5 years and visit recorded within ± 6 months. Hazard ratios (HR) were estimated using Cox models adjusted for age and smoking status and pooled across databases by random effects meta-analyses. RESULTS: Out of 18,782,281 adults, we identified 136,703 patients with coded NAFLD/NASH. Coded NAFLD/NASH patients were more likely to have diabetes, hypertension and obesity than matched controls. HR for cirrhosis in patients compared to controls was 4.73 (95% CI 2.43-9.19) and for HCC, 3.51 (95% CI 1.72-7.16). HR for either outcome was higher in patients with NASH and those with high-risk Fib-4 scores. The strongest independent predictor of a diagnosis of HCC or cirrhosis was baseline diagnosis of diabetes. CONCLUSIONS: Real-world population data show that recorded diagnosis of NAFLD/NASH increases risk of life-threatening liver outcomes. Diabetes is an independent predictor of advanced liver disease diagnosis, emphasising the need to identify specific groups of patients at highest risk.

Fluorescent cell tracer dye permits real-time assessment of re-epithelialization in a serum-free ex vivo human skin wound assay.

Ex vivo wounded human skin organ culture is an invaluable tool for translationally relevant preclinical wound healing research. However, studies incorporating this system are still underutilized within the field because of the low throughput of histological analysis required for downstream assessment. In this study, we use intravital fluorescent dye to lineage trace epidermal cells, demonstrating that wound re-epithelialization of human ex vivo wounds occurs consistent with an extending shield mechanism of collective migration. Moreover, we also report a relatively simple method to investigate global epithelial closure of explants in culture using daily fluorescent dye treatment and en face imaging. This study is the first to quantify healing of ex vivo wounds in a longitudinal manner, providing global assessments for re-epithelialization and tissue contraction. We show that this approach can identify alterations to healing with a known healing promoter. This methodological study highlights the utility of human ex vivo wounds in enhancing our understanding of mechanisms of human skin repair and in evaluating novel therapies to improve healing outcome.

Axillary traction: An effective method of resolving shoulder dystocia.

BACKGROUND: At Counties Manukau Health in Auckland, New Zealand, axillary traction is being used when an internal manoeuvre is required for resolution of shoulder dystocia. AIMS: This study presents the outcomes for mother and baby from use of axillary traction and other internal manoeuvres. MATERIALS AND METHODS: Retrospective review of the clinical records of mother and baby for all labours complicated by shoulder dystocia was carried out for an eight-year period. Maternal and neonatal information were compared for the three cohorts of the first internal manoeuvre documented: axillary traction, posterior arm delivery and rotational manoeuvres. RESULTS: There were 226 women who required the use of internal manoeuvres with no significant differences in age, body mass index, parity, ethnicity, diabetes incidence, induction and augmentation of labour rates, length of the first stage and birth weight between the cohorts. Axillary traction was the first internal manoeuvre used for 119 (52.7%) with a success rate of 95.8%. Posterior arm delivery was used first for 49 (21.7%) women with a success rate of 85.7%. Rotational manoeuvres were used first for 58 (25.7%) women with a statistically inferior success rate of 48.3%. There was no significant difference in the maternal and neonatal complication rates between the cohorts. CONCLUSION: Axillary traction has been utilised as the first internal manoeuvre for a large number of women with a higher success rate than other internal manoeuvres without any increase in maternal or neonatal morbidity. It is recommended that this be the first internal manoeuvre attempted when shoulder dystocia occurs.

Real-world data reveal a diagnostic gap in non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide. It affects an estimated 20% of the general population, based on cohort studies of varying size and heterogeneous selection. However, the prevalence and incidence of recorded NAFLD diagnoses in unselected real-world health-care records is unknown. We harmonised health records from four major European territories and assessed age- and sex-specific point prevalence and incidence of NAFLD over the past decade. METHODS: Data were extracted from The Health Improvement Network (UK), Health Search Database (Italy), Information System for Research in Primary Care (Spain) and Integrated Primary Care Information (Netherlands). Each database uses a different coding system. Prevalence and incidence estimates were pooled across databases by random-effects meta-analysis after a log-transformation. RESULTS: Data were available for 17,669,973 adults, of which 176,114 had a recorded diagnosis of NAFLD. Pooled prevalence trebled from 0.60% in 2007 (95% confidence interval: 0.41-0.79) to 1.85% (0.91-2.79) in 2014. Incidence doubled from 1.32 (0.83-1.82) to 2.35 (1.29-3.40) per 1000 person-years. The FIB-4 non-invasive estimate of liver fibrosis could be calculated in 40.6% of patients, of whom 29.6-35.7% had indeterminate or high-risk scores. CONCLUSIONS: In the largest primary-care record study of its kind to date, rates of recorded NAFLD are much lower than expected suggesting under-diagnosis and under-recording. Despite this, we have identified rising incidence and prevalence of the diagnosis. Improved recognition of NAFLD may identify people who will benefit from risk factor modification or emerging therapies to prevent progression to cardiometabolic and hepatic complications.

A guide to studying human dermal adipocytes in situ.

Dermal white adipose tissue (DWAT) is a main component of human skin, composed of individual lipid-laden mesenchymal cells known as dermal adipocytes (DAs). Besides their well-known role in lipid storage and release, DAs also promote skin immunity, wound healing and hair follicle cycling and are important players in cutaneous neuroendocrinology. The ever-growing insights into DWAT functions, albeit mostly in mice, have invited speculation that it may be involved in multiple skin diseases ranging from fibrosis to alopecia and psoriasis, thus designating human DWAT a clinically relevant, but as yet insufficiently investigated skin compartment. Therefore, this practical, user-friendly guide aims to introduce the techniques available to study human DWAT in situ and ex vivo, including immunohistochemistry, immunofluorescence microscopy and analysis via quantitative immunohistomorphometry. Here, we provide information on a collection of stains comprising pre-adipocyte (Pref1) and mature adipocyte markers (Perilipin1, Caveolin1), as well as various lipid (OilRedO, BODIPY) and histochemical stains (H&E, trichrome) available for use on human DWAT. We offer the reader guidelines on fixing, processing and staining human DAs and highlight caveats and solutions to common problems that one may encounter when studying this fascinating skin compartment. We also suggest standard methods for conducting quantitative immunohistomorphometry on human DWAT and its individual adipocytes to quantify cell size, number, lipid content and fluorescence intensity of adipose-specific markers. Finally, we briefly introduce in situ hybridization, transmission electron microscopy and essentials of magnetic resonance imaging imaging as additional tools for instructively interrogating this largest, but still least-known compartment of human skin.

Linking individual-level data on diagnoses and dispensing for research on antibiotic use: Evaluation of a novel data source from English secondary care.

PURPOSE: There has been a focus on stewardship programmes to curb inappropriate antibiotic prescribing and reduce antimicrobial resistance. In-hospital, patient-level prescribing linked to indication is needed to support surveillance, evaluation of stewardship initiatives, as well as other antibiotic research. We evaluated whether a novel dataset linking hospital pharmacy records to Hospital Episode Statistics data can be used for antibiotic research. METHODS: Using the Hospital Treatment Insights (HTI) database, which links Hospital Episode Statistics to pharmacy records from 43 out of 153 hospital trusts in England, we estimated the proportion of missed linkage and identified characteristics associated with missing data. RESULTS: Linkage of antibiotics to patients was inconsistent and dependent on drug type and clinical setting, so that linkage for some specific antibiotics was high (80-100%), but overall, only 27.6% (CI: 27.4%-27.8%) for all antibiotics dispensed. Linkage was best for quinolones (62.6%; CI: 61.8%-63.8%), but only 21.1% (CI: 21.1%-21.2%) for penicillins. Linkage was lower for common antibiotics and in emergency departments; however, 80% linkage was achieved for individual drugs like clindamycin, especially on wards with reduced ward stock use. CONCLUSIONS: For those antibiotics with high linkage, HTI might be used to study associations between indication, dispensing, and outcomes. However, the majority of common antibiotics had insufficient linkage, likely due to extensive use of ward stocks. Therefore, HTI in its current form is not suitable for general antibiotic surveillance or evaluation of stewardship initiatives. For drugs in HTI other than antibiotics, linkage should be similarly evaluated before a study is conducted.

Changes in the racial disparity in breast cancer mortality in the ten US cities with the largest African American populations from 1999 to 2013: The reduction in breast cancer mortality disparity in Chicago.

PURPOSE: Assess progress made to reduce racial disparity in breast cancer mortality in Chicago compared to nine other cities with largest African American populations and the US. METHODS: The Non-Hispanic Black (NHB) and Non-Hispanic White (NHW) female breast cancer mortality rates and rate ratios (RR) (disparity) were compared between 1999 and 2005 and 2006 and 2013. RESULTS: Between the two periods, the NHB breast cancer mortality rate in Chicago decreased by 13.9% (95% CI [-13.81, -13.92] compared to 7.7% (95% CI [-7.52, -7.83]) for NHW. A drop of 20% in the disparity was observed, from 51% (RR: 1.51, 95% CI [-7.52, -7.83]) to 41% (RR: 1.41, 95% CI [1.30, 1.52]). Whereas from 1999 to 2005 Chicago's disparity was above that of the U.S., from 2006 to 2013, it is now slightly lower. For the remaining nine cities and the US, the mortality disparity either grew or remained the same. CONCLUSIONS: Chicago's improvement in NHB breast cancer mortality and disparity reduction occurred in the context of city-wide comprehensive public health initiatives and shows promise as a model for other cities with high health outcome disparities.

Hair Follicle Bulge Stem Cells Appear Dispensable for the Acute Phase of Wound Re-epithelialization.

The cutaneous healing response has evolved to occur rapidly, in order to minimize infection and to re-establish epithelial homeostasis. Rapid healing is achieved through complex coordination of multiple cell types, which importantly includes specific cell populations within the hair follicle (HF). Under physiological conditions, the epithelial compartments of HF and interfollicular epidermis remain discrete, with K15(+ve) bulge stem cells contributing progeny for HF reconstruction during the hair cycle and as a basis for hair shaft production during anagen. Only upon wounding do HF cells migrate from the follicle to contribute to the neo-epidermis. However, the identity of the first-responding cells, and in particular whether this process involves a direct contribution of K15(+ve) bulge cells to the early stage of epidermal wound repair remains unclear. Here we demonstrate that epidermal injury in murine skin does not induce bulge activation during early epidermal wound repair. Specifically, bulge cells of uninjured HFs neither proliferate nor appear to migrate out of the bulge niche upon epidermal wounding. In support of these observations, Diphtheria toxin-mediated partial ablation of K15(+ve) bulge cells fails to delay wound healing. Our data suggest that bulge cells only respond to epidermal wounding during later stages of repair. We discuss that this response may have evolved as a protective safeguarding mechanism against bulge stem cell exhaust and tumorigenesis. Stem Cells 2016;34:1377-1385.

The battle of the bulge: re-evaluating hair follicle stem cells in wound repair.

The hair follicle has an established role in wound re-epithelialisation, a phenomenon that has been appreciated since at least the first half of the last century. The bulge niche, one location of hair follicle epithelial stem cells has been of particular interest to researchers over recent years, with numerous studies showing its ability to directly contribute to epidermal repair. However, recent work has highlighted other progenitor regions of the hair follicle that appear to act as stem cells during epidermal repair. In addition, several studies within the last 12 months have questioned the importance of the bulge during re-epithelialisation, producing conflicting literature. Here we provide a new model to demonstrate how several important differences in experimental design between studies could account for these seemingly opposing findings, which may have implications for how future studies are conducted.

Recall and Cancer Detection Rates for Screening Mammography: Finding the Sweet Spot.

OBJECTIVE: The purpose of this study is to identify the optimal screening mammography recall rate range on the basis of cancer detection rates among breast imaging specialists at an academic institution. MATERIALS AND METHODS: Medical outcome audit data collected in accordance with the Mammography Quality Standards Act from September 1, 2007, through August 31, 2012, were reviewed. Cancer detection rates were calculated from 984 screen-detected cancers identified in 188,959 total digital screening mammograms. The percentages of minimally invasive and early-stage cancers were also calculated. The 75 annual recall rates were analyzed two ways. First, they were separated into recall groups to assess cancer detection rate variation by the recall categories using rate ratios: less than 10%, 10% to less than 12%, 12% to less than 14%, and 14% or higher. Next, a linear regression with bootstrap bias correction was performed to assess changes in cancer detection rate with each unit increase in the recall rate up to 20%, with the recall category of less than 7% taken as reference. Annual cancer detection rates for a physician were grouped according to annual percentage recall rate. RESULTS: Statistically significantly higher cancer detection rates were seen for recall rates 12% or higher, with rate ratios of 1.75 (95% CI, 1.40-2.19) and 2.06 (95% CI, 1.72-2.46) for the recall groups 12% to less than 14% and 14% and higher, respectively, compared with the less than 10% group. When taking the category 12% to less than 14% as the reference, there were no statistically significant differences between recall groups 12% to less than 14% and 14% or higher in cancer detection rate. A statistically significant increase in the cancer detection rate with each unit increase in the recall rate was seen only for recall rates 12% or higher. CONCLUSION: These observations suggest that the sweet spot for optimal cancer detection is in the recall rate range 12% to less than 14% with the incremental benefit above this to be relatively small. A recall rate less than 10% may be too low.

Oestrogen promotes healing in a bacterial LPS model of delayed cutaneous wound repair.

Wound infection is a major clinical problem, yet understanding of bacterial host interactions in the skin remains limited. Microbe-derived molecules, known as pathogen-associated molecular patterns, are recognised in barrier tissues by pattern-recognition receptors. In particular, the pathogen-associated molecular pattern, lipopolysaccharide (LPS), a component of microbial cell walls and a specific ligand for Toll-like receptor 4, has been widely used to mimic systemic and local infection across a range of tissues. Here we administered LPS derived from Klebsiella pneumoniae, a species of bacteria that is emerging as a wound-associated pathogen, to full-thickness cutaneous wounds in C57/BL6 mice. Early in healing, LPS-treated wounds displayed increased local apoptosis and reduced proliferation. Subsequent healing progression was delayed with reduced re-epithelialisation, increased proliferation, a heightened inflammatory response and perturbed wound matrix deposition. Our group and others have previously demonstrated the beneficial effects of 17ß-estradiol treatment across a range of preclinical wound models. Here we asked whether oestrogen would effectively promote healing in our LPS bacterial infection model. Intriguingly, co-treatment with 17ß-estradiol was able to promote re-epithelialisation, dampen inflammation and induce collagen deposition in our LPS-delayed healing model. Collectively, these studies validate K. pneumoniae-derived LPS treatment as a simple yet effective model of bacterial wound infection, while providing the first indication that oestrogen could promote cutaneous healing in the presence of infection, further strengthening the case for its therapeutic use.

Consumer Rankings and Health Care: Toward Validation and Transparency.

BACKGROUND: Differences between the Centers for Medicare & Medicaid Services (CMS)-measured rates of safety events for Rush University Medical Center (RUMC; Chicago) and the U. S. News & World Report (USNWR)-deter mined patient safety score were evaluated in an attempt to validate the USNWR patient safety score-based ranking. METHODS: The USNWR findings for Patient Safety Indicators (PSIs) were compared with findings derived from RUMC internal billing data, and sensitivity analyses were conducted using a simulated data set derived from the Healthcare Cost and Utilization Project (HCUP) state inpatient data sets. RESULTS: Discrepancies were found for PSIs 3 (Pressure Ulcer Rate), 9 (Perioperative Hemorrhage or Hematoma Rate), and 11 (Postoperative Respiratory Failure Rate)-an excess of 0.72, 0.63, and 0.26 cases/1,000 admissions, in USNWR versus RUMC, respectively). The sensitivity analysis, which included missing present on admission (POA) flags and dates, resulted in an increase of rates by 1.83 (95% confidence interval [CI] = 1.10-2.56) cases/1,000 hospital- izations, 2.72 (CI = 0.00-5.90) cases/1,000 hospitalizations, and 3.89 (CI = 1.60-6.20) cases/1,000 hospitalizations for PSI 3, 9, and 11, respectively. Regression modeling showed that each 1% increase in transfers was associated with an in- crease of 0.06 cases of PSI 3/1,000 admissions; each 1,000 increase in admissions was associated with an increase of 0.04 cases of PSI 9/1,000 admissions. CONCLUSION: The USNWR data set produced inaccurate PSI rates for RUMC, and false-positive event rates were more common among high-transfer and high-volume hos- pitals. More transparency and validation is needed for con- sumer-based benchmarking methods. In response to these findings and concerns raised by others, in 2016 USNWR made changes to its methodology and data sources and reported them in announcing its 2016-17 Best Hospitals.

Chicago Ebola Response Network (CERN): A Citywide Cross-hospital Collaborative for Infectious Disease Preparedness.

The 2014-2015 Ebola virus disease (EVD) epidemic and international public health emergency has been referred to as a "black swan" event, or an event that is unlikely, hard to predict, and highly impactful once it occurs. The Chicago Ebola Response Network (CERN) was formed in response to EVD and is capable of receiving and managing new cases of EVD, while also laying the foundation for a public health network that can anticipate, manage, and prevent the next black swan public health event. By sharing expertise, risk, and resources among 4 major academic centers, Chicago created a sustainable network to respond to the latest in a series of public health emergencies. In this respect, CERN is a roadmap for how a region can prepare to respond to public health emergencies, thereby preventing negative impacts through planning and implementation.