SARS-CoV-2 infection increases risk of acute kidney injury in a bimodal age distribution.

BACKGROUND: Hospitalized patients with SARS-CoV2 develop acute kidney injury (AKI) frequently, yet gaps remain in understanding why adults seem to have higher rates compared to children. Our objectives were to evaluate the epidemiology of SARS-CoV2-related AKI across the age spectrum and determine if known risk factors such as illness severity contribute to its pattern. METHODS: Secondary analysis of ongoing prospective international cohort registry. AKI was defined by KDIGO-creatinine only criteria. Log-linear, logistic and generalized estimating equations assessed odds ratios (OR), risk differences (RD), and 95% confidence intervals (CIs) for AKI and mortality adjusting for sex, pre-existing comorbidities, race/ethnicity, illness severity, and clustering within centers. Sensitivity analyses assessed different baseline creatinine estimators. RESULTS: Overall, among 6874 hospitalized patients, 39.6% (n = 2719) developed AKI. There was a bimodal distribution of AKI by age with peaks in older age (≥60 years) and middle childhood (5-15 years), which persisted despite controlling for illness severity, pre-existing comorbidities, or different baseline creatinine estimators. For example, the adjusted OR of developing AKI among hospitalized patients with SARS-CoV2 was 2.74 (95% CI 1.66-4.56) for 10-15-year-olds compared to 30-35-year-olds and similarly was 2.31 (95% CI 1.71-3.12) for 70-75-year-olds, while adjusted OR dropped to 1.39 (95% CI 0.97-2.00) for 40-45-year-olds compared to 30-35-year-olds. CONCLUSIONS: SARS-CoV2-related AKI is common with a bimodal age distribution that is not fully explained by known risk factors or confounders. As the pandemic turns to disproportionately impacting younger individuals, this deserves further investigation as the presence of AKI and SARS-CoV2 infection increases hospital mortality risk.

An Ultrasound Screening Exam During Medicare Wellness Visits May Be Beneficial.

OBJECTIVES: The physical exam component of a periodic health visit in the elderly has not been considered useful. Standard Medicare Wellness visits require no physical exam beyond blood pressure and most physicians perform limited exams during these visits. The objective of this study was to test the feasibility, potential benefit, and costs of performing a screening ultrasound (US) exam during Medicare Wellness visits. METHODS: A physician examiner at an academic internal medicine primary care clinic performed a screening US exam targeting important abnormalities of patients 65-85 years old during a Medicare Wellness visit. The primary care physician (PCP) recorded the follow-up items for each abnormality identified by the US examiner and assessed the benefit of each abnormality for the participant. Abnormality benefit, net exam benefit per participant, follow-up items and costs, participant survey results, and exam duration were assessed. RESULTS: Participants numbered 108. Total abnormalities numbered 283 and new diagnoses were 172. Positive benefit scores were assigned to 38.8%, neutral (zero) scores to 59.4%, and negative benefit scores to 1.8% of abnormalities. Net benefit scores per participant were positive in 63.9%, 0 in 34.3%, and negative in 1.8%. Follow-up items were infrequent resulting in 76% of participants without follow-up cost. Participant survey showed excellent acceptance of the exam. CONCLUSIONS: The US screening exam identified frequent abnormalities in Medicare Wellness patients. The assessed benefits were rarely negative and often mild to moderately positive, with important new chronic conditions identified. Follow-up costs were low when the PCPs were also US experts.

Outcomes of Patients With Coronavirus Disease 2019 Receiving Organ Support Therapies: The International Viral Infection and Respiratory Illness Universal Study Registry.

OBJECTIVES: To describe the outcomes of hospitalized patients in a multicenter, international coronavirus disease 2019 registry. DESIGN: Cross-sectional observational study including coronavirus disease 2019 patients hospitalized with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection between February 15, 2020, and November 30, 2020, according to age and type of organ support therapies. SETTING: About 168 hospitals in 16 countries within the Society of Critical Care Medicine's Discovery Viral Infection and Respiratory Illness University Study coronavirus disease 2019 registry. PATIENTS: Adult hospitalized coronavirus disease 2019 patients who did and did not require various types and combinations of organ support (mechanical ventilation, renal replacement therapy, vasopressors, and extracorporeal membrane oxygenation). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome was hospital mortality. Secondary outcomes were discharge home with or without assistance and hospital length of stay. Risk-adjusted variation in hospital mortality for patients receiving invasive mechanical ventilation was assessed by using multilevel models with hospitals as a random effect, adjusted for age, race/ethnicity, sex, and comorbidities. Among 20,608 patients with coronavirus disease 2019, the mean (± sd) age was 60.5 (±17), 11,1887 (54.3%) were men, 8,745 (42.4%) were admitted to the ICU, and 3,906 (19%) died in the hospital. Hospital mortality was 8.2% for patients receiving no organ support (n = 15,001). The most common organ support therapy was invasive mechanical ventilation (n = 5,005; 24.3%), with a hospital mortality of 49.8%. Mortality ranged from 40.8% among patients receiving only invasive mechanical ventilation (n =1,749) to 71.6% for patients receiving invasive mechanical ventilation, vasoactive drugs, and new renal replacement therapy (n = 655). Mortality was 39% for patients receiving extracorporeal membrane oxygenation (n = 389). Rates of discharge home ranged from 73.5% for patients who did not require organ support therapies to 29.8% for patients who only received invasive mechanical ventilation, and 8.8% for invasive mechanical ventilation, vasoactive drugs, and renal replacement; 10.8% of patients older than 74 years who received invasive mechanical ventilation were discharged home. Median hospital length of stay for patients on mechanical ventilation was 17.1 days (9.7-28 d). Adjusted interhospital variation in mortality among patients receiving invasive mechanical ventilation was large (median odds ratio 1.69). CONCLUSIONS: Coronavirus disease 2019 prognosis varies by age and level of organ support. Interhospital variation in mortality of mechanically ventilated patients was not explained by patient characteristics and requires further evaluation.

Outcomes in reported penicillin allergic mothers and neonates requiring Group B streptococcal prophylaxis: a retrospective observational cohort study.

BACKGROUND: Infectious morbidity and mortality in the first week of life is commonly caused by early-onset neonatal Group B streptococcus (GBS) disease. This infection is spread from GBS positive mothers to neonates by vertical transmission during delivery and results in serious illness for newborns. Intrapartum prophylactic antibiotics have decreased the incidence of early-onset neonatal GBS disease by 80%. Patients labeled with a penicillin allergy (PcnA) alternatively receive either vancomycin or clindamycin but effectiveness is controversial. We evaluated the influence of a reported PcnA label versus no PcnA label on inpatient maternal and neonatal outcomes. METHODS: Our goal was to examine the relationship between a PcnA label, maternal and neonatal outcomes, and hospital costs. We collected retrospective data with institutional IRB approval from 2016 - 2018 for hospitalized patients who were GBS positive, pregnant at time of admission, ≥ 18 years of age, received antibiotic prophylaxis for GBS, were labeled as PcnA or non-PcnA, and completed a vaginal delivery. Patient characteristics and maternal/neonatal outcomes were examined. Statistical tests included calculations of means, medians, proportions, Mann-Whitney, two-sample t-tests, Chi-squared or Fisher's Exact tests, and generalized linear and logistic regression models. Significance was set at p < 0.05. RESULTS: Most PcnA patients were white, older, had a higher median body mass index and mean heart rate, and a greater proportion used tobacco than non-PcnA patients. In regression analyses, PcnA hospitalized patients received a shorter duration of antibiotic treatment than non-PcnA patients [incidence rate ratio (IRR): 0.45, 95% CI: 0.38-0.53]. PcnA patients were also more likely to have their baby's hospital LOS be > 48 h [adjusted odds ratio (AOR): 1.35, 95% CI: 1.07-1.69] even though the PcnA mothers' LOS was not different from non-PcnA mothers. Cost of care, mortality, intensive care, median parity, mean gravidity, and miscarriage were similar between the groups. CONCLUSIONS: In hospitalized obstetric patients, a PcnA label was associated with a shorter maternal course of antibiotic treatment and a longer neonatal LOS. Further prospective studies are needed to clarify the underlying reasons for these outcomes.

Comparative Performance of Pulmonary Ultrasound, Chest Radiograph, and CT Among Patients With Acute Respiratory Failure.

OBJECTIVES: The study goal was to concurrently evaluate agreement of a 9-point pulmonary ultrasound protocol and portable chest radiograph with chest CT for localization of pathology to the correct lung and also to specific anatomic lobes among a diverse group of intubated patients with acute respiratory failure. DESIGN: Prospective cohort study. SETTING: Medical, surgical, and neurologic ICUs at a 670-bed urban teaching hospital. PATIENTS: Intubated adults with acute respiratory failure having chest CT and portable chest radiograph performed within 24 hours of intubation. INTERVENTIONS: A 9-point pulmonary ultrasound examination performed at the time of intubation. MEASUREMENTS AND MAIN RESULTS: Sixty-seven patients had pulmonary ultrasound, portable chest radiograph, and chest CT performed within 24 hours of intubation. Overall agreement of pulmonary ultrasound and portable chest radiograph findings with correlating lobe ("lobe-specific" agreement) on CT was 87% versus 62% (p < 0.001), respectively. Relaxing the agreement definition to a matching CT finding being present anywhere within the correct lung ("lung-specific" agreement), not necessarily the specific mapped lobe, showed improved agreement for both pulmonary ultrasound and portable chest radiograph respectively (right lung: 92.5% vs 65.7%; p < 0.001 and left lung: 83.6% vs 71.6%; p = 0.097). The highest lobe-specific agreement was for the finding of atelectasis/consolidation for both pulmonary ultrasound and portable chest radiograph (96% and 73%, respectively). The lowest lobe-specific agreement for pulmonary ultrasound was normal lung (79%) and interstitial process for portable chest radiograph (29%). Lobe-specific agreement differed most between pulmonary ultrasound and portable chest radiograph for interstitial findings (86% vs 29%, respectively). Pulmonary ultrasound had the lowest agreement with CT for findings in the left lower lobe (82.1%). Pleural effusion agreement also differed between pulmonary ultrasound and portable chest radiograph (right: 99% vs 87%; p = 0.009 and left: 99% vs 85%; p = 0.004). CONCLUSIONS: A clinical, 9-point pulmonary ultrasound protocol strongly agreed with specific CT findings when analyzed by both lung- and lobe-specific location among a diverse population of mechanically ventilated patients with acute respiratory failure; in this regard, pulmonary ultrasound significantly outperformed portable chest radiograph.

Retrospective Analysis of the Effect of Postdischarge Telephone Calls by Hospitalists on Improvement of Patient Satisfaction and Readmission Rates.

OBJECTIVES: The influence of postdischarge telephone call interventions preventing hospital readmissions is unclear. A novel approach of the discharging hospitalist providing this intervention may improve overall patient satisfaction. Our objective was to assess the impact of postdischarge telephone calls from discharging hospitalists on readmissions and patients' ratings of hospital care and hospitalist communication. METHODS: Data were retrospectively collected from patients' electronic health records at a 167-bed hospital in Fridley, Minnesota and the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey. Patients were 18 years old or older and diagnosed as having nonpsychiatric conditions. Telephone calls were made by the discharging hospitalist to adult patients discharged to home with or without home care services between February 28, 2015 and February 29, 2016. Multivariate logistic regression models were used to evaluate associations of postdischarge telephone calls with global hospital care rating and hospitalist communication from HCAHPS, and 30-day readmission rates from electronic health records. RESULTS: Of 4490 eligible patients, 1067 had completed telephone calls (23.8%). The intervention was associated with a statistically significant improvement in the responses to HCAHPS overall hospital rating and HCAHPS doctor communication questions (adjusted odds ratio 1.52, P = 0.04 and adjusted odds ratio 1.56, P = 0.021) that varied by patient age at first admission (P = 0.001 and P = 0.101). With longer inpatient lengths of stay, 30-day readmission rates improved after patients received a postdischarge telephone call, but this outcome was not statistically significant. CONCLUSIONS: This study revealed that postdischarge telephone calls from discharging hospitalists increased patient satisfaction. Further research is needed to understand the causal relationships among the intervention, 30-day hospital readmission rates, and inpatient length of stay.

Adherence to treatment guidelines: the association between stroke risk stratified comparing CHADS2 and CHA2DS2-VASc score levels and warfarin prescription for adult patients with atrial fibrillation.

BACKGROUND: Ischemic stroke is a risk associated with atrial fibrillation (AF) and is estimated to occur five times more often in afflicted patients than in those without AF. Anti-thrombotic therapy is recommended for the prevention of ischemic stroke. Risk stratification tools, such as the CHADS2, and more recently the CHA2DS2-VASc, for predicting stroke in patients with AF have been developed to determine the level of stroke risk and assist clinicians in the selection of antithrombotic therapy. Warfarin, for stroke prevention in AF, is the most commonly prescribed anticoagulant in North America. The purpose of this study was to examine the utility of using the CHADS2 score levels (low and high) in contrast to the CHA2DS2-VASc when examining the outcome of warfarin prescriptions for adult patients with AF. The CHA2DS2-VASc tool was not widely used in 2010, when the data analyzed were collected. It has only been since 2014 that CHA2DS2-VASc criteria has been recommended to guide anticoagulant treatment in updated AF treatment guidelines. METHODS: Bivariate and multivariate data analysis strategies were used to analyze 2010 National Ambulatory Care Survey (NAMCS) data. NAMCS is designed to collect data on the use and provision of ambulatory care services nationwide. The study population for this research was US adults with a diagnosis of AF. Warfarin prescription was the dependent variable for this study. The study population was 7,669,844 AF patients. RESULTS: Bivariate analysis revealed that of those AF patients with a high CHADS2 score, 25.1% had received a warfarin prescription and 18.8 for those with a high CHA2DS2-VASc score. Logistic regression analysis yielded that patients with AF had higher odds of having a warfarin prescription if they had a high CHADS2 score, were Caucasian, lived in a zip code where < 20% of the population had a university education, and lived in a zip code where < 10% of the population were living in households with incomes below the federal poverty level. Further, the analysis yielded that patients with AF had lesser odds of having a warfarin prescription if they were ≥ 65 years of age, female, or had health insurance. CONCLUSIONS: Overall, warfarin appears to be under-prescribed for patients with AF regardless of the risk stratification system used. Based on the key findings of our study opportunities for interventions are present to improve guideline adherence in alignment with risk stratification for stroke prevention. Interprofessional health care teams can provide improved medical management of stroke prevention for patients with AF. These interprofessional health care teams should be constituted of primary care providers (physicians, physician assistants, and nurse practitioners), nurses (RN, LPN), and pharmacists (PharmD, RPh).

Potentially Inappropriate Medication Prescribing in U.S. Older Adults with Selected Chronic Conditions.

OBJECTIVE: Developing one or more chronic diseases increases with age. Appropriate treatment for chronic conditions often requires multiple medications. The purpose of this study was to examine potentially inappropriate prescriptions in patients 65 years of age or older, seen in a primary care office, with at least one of three chronic conditions (diabetes, arthritis, depression), who were prescribed at least two medications, one of which was inappropriate for the patient's condition. DESIGN: 2012 National Ambulatory Medical Care Survey data were examined using multivariate techniques. SETTING: U.S. primary care office visits. MAIN OUTCOME MEASURES: Drug appropriateness was ascertained from practice guidelines. Potentially inappropriate medications were ascertained from the 2012 Beers criteria. The 2012 Beers criteria were used since the data analyzed were from 2012. RESULTS: Logistic regression analysis yielded that older adults with diabetes had greater odds of having a potentially inappropriate prescription if they saw a provider in a rural setting, were non-white, had health insurance, and had two or more office visits in the last 12 months. CONCLUSION: There is a need to address prescribing of potentially inappropriate medications to older, non-white patients who have diabetes. Living in rural areas is also an important factor in prescribing patterns for older adults with diabetes. Our findings suggest that interventions are warranted to address this health problem. One solution is the establishment of interprofessional and multidisciplinary teams of health care providers constituted of prescribers and nonprescribers to comprehensively evaluate prescribing practices.

Increased expression of GCNT1 is associated with altered O-glycosylation of PSA, PAP, and MUC1 in human prostate cancers.

BACKGROUND: Protein glycosylation is a common posttranslational modification and glycan structural changes have been observed in several malignancies including prostate cancer. We hypothesized that altered glycosylation could be related to differences in gene expression levels of glycoprotein synthetic enzymes between normal and malignant prostate tissues. METHODS: We interrogated prostate cancer gene expression data for reproducible changes in expression of glycoprotein synthetic enzymes. Over-expression of GCNT1 was validated in prostate samples using RT-PCR. ELISA was used to measure core 2 O-linked glycan sialyl Lewis X (sLe(x) ) of prostate specific antigen (PSA), Mucin1 (MUC1), and prostatic acidic phosphatase (PAP) proteins. RESULTS: A key glycosyltransferase, GCNT1, was consistently over-expressed in several prostate cancer gene expression datasets. RT-PCR confirmed increased transcript levels in cancer samples compared to normal prostate tissue in fresh-frozen prostate tissue samples. ELISA using PSA, PAP, and MUC1 capture antibodies and a specific core 2 O-linked sLe(x) detection antibody demonstrated elevation of this glycan structure in cancer compared to normal tissues for MUC1 (P = 0.01), PSA (P = 0.03) and near significant differences in PAP sLe(x) levels (P = 0.06). MUC1, PSA and PAP protein levels alone were not significantly different between paired normal and malignant prostate samples. CONCLUSIONS: GCNT1 is over-expressed in prostate cancer and is associated with higher levels of core 2 O-sLe(x) in PSA, PAP and MUC1 proteins. Alterations of O-linked glycosylation could be important in prostate cancer biology and could provide a new avenue for development of prostate cancer specific glycoprotein biomarkers.

Opioid prescribing patterns for non-malignant chronic pain for rural versus non-rural US adults: a population-based study using 2010 NAMCS data.

BACKGROUND: Non-malignant chronic pain (NMCP) is one of the most common reasons for primary care visits. Pain management health care disparities have been documented in relation to patient gender, race, and socioeconomic status. Although not studied in relation to chronic pain management, studies have found that living in a rural community in the US is associated with health care disparities. Rurality as a social determinant of health may influence opioid prescribing. We examined rural and non-rural differences in opioid prescribing patterns for NMCP management, hypothesizing that distinct from education, income, racial or gender differences, rural residency is a significant and independent factor in opioid prescribing patterns. METHODS: 2010 National Ambulatory Medical Care Survey (NAMCS) data were examined using bivariate and multivariate techniques. NAMCS data were collected using a multi-stage sampling strategy. For the multivariate analysis performed the SPSS complex samples algorithm for logistic regression was used. RESULTS: In 2010 an estimated 9,325,603 US adults (weighted from a sample of 2745) seen in primary care clinics had a diagnosis of NMCP; 36.4% were prescribed an opioid. For US adults with a NMCP diagnosis bivariate analysis revealed rural residents had higher odds of having an opioid prescription than similar non-rural adults (OR = 1.515, 95% CI 1.513-1.518). Complex samples logistic regression analysis confirmed the importance of rurality and yielded that US adults with NMCP who were prescribed an opioid had higher odds of: being non-Caucasian (AOR =2.459, 95% CI 1.194-5.066), and living in a rural area (AOR =2.935, 95% CI 1.416-6.083). CONCLUSIONS: Our results clearly indicated that rurality is an important factor in opioid prescribing patterns that cannot be ignored and bears further investigation. Further research on the growing concern about the over-prescribing of opioids in the US should now include rurality as a variable in data generation and analysis. Future research should also attempt to document the ecological, sociological and political factors impacting opioid prescribing and care in rural communities. Prescribers and health care policy makers need to critically evaluate the implications of our findings and their relationship to patient needs, best practices in a rural setting, and the overall consequences of increased opioid prescribing on rural communities.

Outcomes in hospitalised patients with sepsis, severe sepsis or septic shock and reported penicillin allergy: a retrospective cohort study.

OBJECTIVE: To determine outcomes in hospitalised patients with sepsis and reported penicillin allergy (PcnA). DESIGN: Observational retrospective cohort study using data from electronic health records. SETTING: A large single health system with 11 hospitals of small, medium and large sizes including a 630-bed tertiary care teaching hospital. PARTICIPANTS: Patients (n=5238) ≥18 years of age, hospitalised with sepsis, severe sepsis or septic shock between 1 January 2016 and 31 December 2018, received antibacterial agents, and had documented PcnA status. Patients <18 years of age at admission were excluded. OUTCOME MEASURES: Primary outcomes evaluated were inpatient mortality and 30-day mortality posthospital discharge. Secondary outcomes were hospital length of stay, 30-day readmissions, duration of antibiotic use, rate of Clostridium difficile infection and total cost of care. RESULTS: There was no difference in outcomes including inpatient or 30-day mortality, hospital length of stay, in-hospital antibiotic duration, C. difficile infection, total cost of care and 30-day readmission rate between patients labelled with a PcnA vs patients who did not report PcnA (non-PcnA). CONCLUSION: In this retrospective single health system study, there was no difference in key outcomes including inpatient or 30-day mortality in patients admitted with sepsis and reported PcnA compared with patients who reported no PcnA.

Outcomes of Minnesota Detoxification Scale (MINDS) Assessment With High-Dose Front Loading Diazepam Treatment for Alcohol Withdrawal in Hospitalized Patients.

BACKGROUND: Benzodiazepines are the gold standard for alcohol withdrawal treatment but choice and dosing vary widely. In 2015, our institution implemented a Minnesota detoxification scale (MINDS) and single standardized high-dose diazepam based protocol for treatment of alcohol withdrawal to replace multiple Clinical Institute Withdrawal Assessment for Alcohol (CIWA) based protocols using lower dose benzodiazepines. We compared use of MINDS versus CIWA assessment protocols with high front loading diazepam treatment in care of patient experiencing alcohol withdrawal during hospitalization. METHODS: Retrospective cohort study of hospitalized patients experiencing alcohol withdrawal to statistically analyze difference in outcomes between CIWA based lower benzodiazepine dose protocols used in 2013-2015 versus the MINDS based high-dose front-loading diazepam protocol used in 2015-2017. RESULTS: Patients treated with MINDS based high dose diazepam protocol were less likely to have physical restraints used (AOR = 0.8, CI: 0.70-0.92), had a shorter hospital length of stay, and fewer days on benzodiazepines (p < 0.001). Patients were more likely to be readmitted to the hospital within 30 days (AOR = 1.13, CI: 1.03-1.26) in MINDS based diazepam treatment group. Total diazepam equivalent dosing was similar in both groups. Mortality rates and ICU use rates were similar between the groups. CONCLUSIONS: Higher dose front loading long acting benzodiazepine can be safely used with beneficial outcomes in hospitalized alcohol withdrawal patients.

Association of latitude and altitude with adverse outcomes in patients with COVID-19: The VIRUS registry.

BACKGROUND: The coronavirus disease 2019 (COVID-19) course may be affected by environmental factors. Ecological studies previously suggested a link between climatological factors and COVID-19 fatality rates. However, individual-level impact of these factors has not been thoroughly evaluated yet. AIM: To study the association of climatological factors related to patient location with unfavorable outcomes in patients. METHODS: In this observational analysis of the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study: COVID-19 Registry cohort, the latitudes and altitudes of hospitals were examined as a covariate for mortality within 28 d of admission and the length of hospital stay. Adjusting for baseline parameters and admission date, multivariable regression modeling was utilized. Generalized estimating equations were used to fit the models. RESULTS: Twenty-two thousand one hundred eight patients from over 20 countries were evaluated. The median age was 62 (interquartile range: 49-74) years, and 54% of the included patients were males. The median age increased with increasing latitude as well as the frequency of comorbidities. Contrarily, the percentage of comorbidities was lower in elevated altitudes. Mortality within 28 d of hospital admission was found to be 25%. The median hospital-free days among all included patients was 20 d. Despite the significant linear relationship between mortality and hospital-free days (adjusted odds ratio (aOR) = 1.39 (1.04, 1.86), P = 0.025 for mortality within 28 d of admission; aOR = -1.47 (-2.60, -0.33), P = 0.011 for hospital-free days), suggesting that adverse patient outcomes were more common in locations further away from the Equator; the results were no longer significant when adjusted for baseline differences (aOR = 1.32 (1.00, 1.74), P = 0.051 for 28-day mortality; aOR = -1.07 (-2.13, -0.01), P = 0.050 for hospital-free days). When we looked at the altitude's effect, we discovered that it demonstrated a non-linear association with mortality within 28 d of hospital admission (aOR = 0.96 (0.62, 1.47), 1.04 (0.92, 1.19), 0.49 (0.22, 0.90), and 0.51 (0.27, 0.98), for the altitude points of 75 MASL, 125 MASL, 400 MASL, and 600 MASL, in comparison to the reference altitude of 148 m.a.s.l, respectively. P = 0.001). We detected an association between latitude and 28-day mortality as well as hospital-free days in this worldwide study. When the baseline features were taken into account, however, this did not stay significant. CONCLUSION: Our findings suggest that differences observed in previous epidemiological studies may be due to ecological fallacy rather than implying a causal relationship at the patient level.

Neutrophil interactions with sialyl Lewis X on human nonsmall cell lung carcinoma cells regulate invasive behavior.

BACKGROUND: The carbohydrate sialyl Lewis X (sLeX) is expressed on leukocytes and carcinoma cells and binds to selectins during inflammatory processes and early metastasis. Synthesis of sLeX depends on activity of enzymes, including α(1,3/1,4) fucosyltransferase (FucT-III). Tumor necrosis factor-α (TNF-α) up-regulates FucT-III, resulting in increased sLeX in the airways of patients with respiratory disease; however, the mechanisms that regulate sLeX in the inflammatory tumor microenvironment are not well understood. METHODS: The authors stably transfected human lung carcinoma cell lines with the FucT-III gene and exposed them to TNF-α to investigate its role in regulation of sLeX expression and selectin-binding ability using semiquantitative real-time polymerase chain reaction and flow cytometry. Cytokine expression was examined in transfected cells using chemiluminescent arrays and enzyme-linked immunosorbent assays, and invasion was studied using Matrigel assays and alterations in morphology. Human lung tissue arrays were analyzed for immunohistochemical detection of sLeX and neutrophils. RESULTS: Stimulation of FucT-III-transfected cells with recombinant human (rh) TNF-α up-regulated sLeX expression and increased E-selectin binding. Transfected cells secreted high levels of interleukin 8, growth-regulated oncogene-α, and mast cell proteinase-1. Cells exposed to rhTNF-α, neutrophil-conditioned media, and cultures with a 5:1 ratio of neutrophils to cancer cells had significantly increased sLeX expression and invasiveness and underwent nonadherent morphologic changes. In lung carcinomas, but not in normal lung tissues, 71% of tumors were highly positive for sLeX expression in areas of increased neutrophil infiltration. CONCLUSIONS: The current results indicated that neutrophils may be recruited to areas of FucT-III activity and sLeX expression in lung carcinomas to enhance the invasive and metastatic potential of lung cancer cells.

Risk Factors for Critical Coronavirus Disease 2019 and Mortality in Hospitalized Young Adults: An Analysis of the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) Coronavirus Disease 2019 Registry.

IMPORTANCE: Even with its proclivity for older age, coronavirus disease 2019 has been shown to affect all age groups. However, there remains a lack of research focused primarily on the young adult population. OBJECTIVES: To describe the epidemiology and outcomes of coronavirus disease 2019 and identify the risk factors associated with critical illness and mortality in hospitalized young adults. DESIGN SETTINGS AND PARTICIPANTS: A retrospective cohort study of the Society of Critical Care Medicine's Viral Infection and Respiratory Illness Universal Study registry. Patients 18-40 years old, hospitalized from coronavirus disease 2019 from March 2020 to April 2021, were included in the analysis. MAIN OUTCOMES AND MEASURES: Critical illness was defined as a composite of mortality and 21 predefined interventions and complications. Multivariable logistic regression was used to assess associations with critical illness and mortality. RESULTS: Data from 4,005 patients (152 centers, 19 countries, 18.6% non-U.S. patients) were analyzed. The median age was 32 years (interquartile range, 27-37 yr); 51% were female, 29.4% Hispanic, and 42.9% had obesity. Most patients (63.2%) had comorbidities, the most common being hypertension (14.5%) and diabetes (13.7%). Hospital and ICU mortality were 3.2% (129/4,005) and 8.3% (109/1,313), respectively. Critical illness occurred in 25% (n = 996), and 34.3% (n = 1,376) were admitted to the ICU. Older age (p = 0.03), male sex (adjusted odds ratio, 1.83 [95% CI, 1.2-2.6]), and obesity (adjusted odds ratio, 1.6 [95% CI, 1.1-2.4]) were associated with hospital mortality. In addition to the above factors, the presence of any comorbidity was associated with critical illness from coronavirus disease 2019. Multiple sensitivity analyses, including analysis with U.S. patients only and patients admitted to high-volume sites, showed similar risk factors. CONCLUSIONS: Among hospitalized young adults, obese males with comorbidities are at higher risk of developing critical illness or dying from coronavirus disease 2019.

Metabolic Syndrome and Acute Respiratory Distress Syndrome in Hospitalized Patients With COVID-19.

Importance: Obesity, diabetes, and hypertension are common comorbidities in patients with severe COVID-19, yet little is known about the risk of acute respiratory distress syndrome (ARDS) or death in patients with COVID-19 and metabolic syndrome. Objective: To determine whether metabolic syndrome is associated with an increased risk of ARDS and death from COVID-19. Design, Setting, and Participants: This multicenter cohort study used data from the Society of Critical Care Medicine Discovery Viral Respiratory Illness Universal Study collected from 181 hospitals across 26 countries from February 15, 2020, to February 18, 2021. Outcomes were compared between patients with metabolic syndrome (defined as ≥3 of the following criteria: obesity, prediabetes or diabetes, hypertension, and dyslipidemia) and a control population without metabolic syndrome. Participants included adult patients hospitalized for COVID-19 during the study period who had a completed discharge status. Data were analyzed from February 22 to October 5, 2021. Exposures: Exposures were SARS-CoV-2 infection, metabolic syndrome, obesity, prediabetes or diabetes, hypertension, and/or dyslipidemia. Main Outcomes and Measures: The primary outcome was in-hospital mortality. Secondary outcomes included ARDS, intensive care unit (ICU) admission, need for invasive mechanical ventilation, and length of stay (LOS). Results: Among 46 441 patients hospitalized with COVID-19, 29 040 patients (mean [SD] age, 61.2 [17.8] years; 13 059 [45.0%] women and 15713 [54.1%] men; 6797 Black patients [23.4%], 5325 Hispanic patients [18.3%], and 16 507 White patients [57.8%]) met inclusion criteria. A total of 5069 patients (17.5%) with metabolic syndrome were compared with 23 971 control patients (82.5%) without metabolic syndrome. In adjusted analyses, metabolic syndrome was associated with increased risk of ICU admission (adjusted odds ratio [aOR], 1.32 [95% CI, 1.14-1.53]), invasive mechanical ventilation (aOR, 1.45 [95% CI, 1.28-1.65]), ARDS (aOR, 1.36 [95% CI, 1.12-1.66]), and mortality (aOR, 1.19 [95% CI, 1.08-1.31]) and prolonged hospital LOS (median [IQR], 8.0 [4.2-15.8] days vs 6.8 [3.4-13.0] days; P < .001) and ICU LOS (median [IQR], 7.0 [2.8-15.0] days vs 6.4 [2.7-13.0] days; P < .001). Each additional metabolic syndrome criterion was associated with increased risk of ARDS in an additive fashion (1 criterion: 1147 patients with ARDS [10.4%]; P = .83; 2 criteria: 1191 patients with ARDS [15.3%]; P < .001; 3 criteria: 817 patients with ARDS [19.3%]; P < .001; 4 criteria: 203 patients with ARDS [24.3%]; P < .001). Conclusions and Relevance: These findings suggest that metabolic syndrome was associated with increased risks of ARDS and death in patients hospitalized with COVID-19. The association with ARDS was cumulative for each metabolic syndrome criteria present.

Tablet vs. station-based laptop ultrasound devices increases internal medicine resident point-of-care ultrasound performance: a prospective cohort study.

BACKGROUND: Point-of-care ultrasound (POCUS) is becoming an important part of internal medicine (IM) residency training. Achieving competency requires performing a large volume of clinical exams which can be difficult within the constraints of residency. Often-cited barriers include insufficient resident time and the interruption of daily workflow. Despite availability of hospital station-based laptop ultrasound machines, we hypothesized that the addition of ward team-based tablet ultrasound devices would lower barriers and increase clinical POCUS volume within an IM residency POCUS curriculum at a 670-bed, quaternary care, teaching hospital. IM resident POCUS volumes and characteristics during an 18-mo. baseline (station-based laptop devices only) period were compared to matched months during the intervention (station-based + tablet). RESULTS: Total patients examined with POCUS by 6 inpatient resident teams during the 18-mo. baseline and intervention periods were 1386 and 1853, respectively. Patients examined per month increased during the intervention by 34% (77 vs. 103, p = 0.002). The number of areas (e.g., abdominal, cardiac) and items (e.g., bladder, pericardial effusion) examined per month increased by 27% (p = 0.021) and 23% (p = 0.073), respectively. CONCLUSIONS: A combined program infrastructure of station-based laptop and "in-the-pocket" tablet ultrasound devices lowered common POCUS barriers of inadequate time and workflow disruption for IM residents and resulted in a meaningful increase of exams within a longitudinal residency-based training program where station-based laptop devices already existed.

Effects of a Consensus-Based Pulmonary Embolism Treatment Algorithm and Response Team on Treatment Modality Choices, Outcomes, and Complications.

Pulmonary embolism (PE) treatment depends on disease severity and risk of complications. Physician and institutional expertise may influence the use of reperfusion therapy (RT) such as systemic thrombolysis (SL) and catheter-directed interventions (CDI). We aimed to investigate the effects of a consensus-based treatment algorithm (TA) and subsequent implementation of PE response team (PERT) on RT modality choices and patient outcomes. A cohort of PE patients admitted to a tertiary care hospital between 2012 and 2017 was retrospectively evaluated. Demographics, clinical variables, RT selections, and patient outcomes during 3 consecutive 2-year periods (baseline, with TA, and with TA+PERT) were compared. Descriptive statistics were used for data analysis. A total of 1105 PE patients were admitted, and 112 received RT. Use of RT increased from 4.7% at baseline to 8.2% and 16.1% during the TA and TA+PERT periods. The primary RT modality transitioned from CDI to SL, and reduced-dose SL became most common. Treatment selection patterns remained unchanged after PERT introduction. Hospital length of stay decreased from 4.78 to 2.96 and 2.81 days (P < .001). Most of the hemorrhagic complications were minor, and their rates were similar across all 3 periods and between SL and CDI. No major hemorrhages occurred in patients treated with reduced-dose SL. In conclusion, TA and PERT represent components of a decision support system facilitating treatment modality selection, contributing to improved outcomes, and limiting complications. Treatment algorithm emerged as a factor providing consistency to PERT recommendations.

The high affinity selectin glycan ligand C2-O-sLex and mRNA transcripts of the core 2 beta-1,6-N-acetylglucosaminyltransferase (C2GnT1) gene are highly expressed in human colorectal adenocarcinomas.

BACKGROUND: The metastasis of cancer cells and leukocyte extravasation into inflamed tissues share common features. Specialized carbohydrates modified with sialyl Lewis x (sLex) antigens on leukocyte membranes are ligands for selectin adhesion molecules on activated vascular endothelial cells at inflammatory sites. The activity of the enzyme core 2 beta1,6 N-acetylglucosaminyltransferase (C2GnT1) in leukocytes greatly increases their ability to bind to endothelial selectins. C2GnT1 is essential for the synthesis of core 2-branched O-linked carbohydrates terminated with sLex (C2-O-sLex). Our goal was to determine the expression profiles of C2-O-sLex in the malignant progression and metastasis of colorectal adenocarcinomas. The well characterized CHO-131 monoclonal antibody (mAb) specifically recognizes C2-O-sLex present in human leukocytes and carcinoma cells. Using CHO-131 mAb, we investigated whether C2-O-sLex was present in 113 human primary colorectal adenocarcinomas, 10 colorectal adenomas, 46 metastatic liver tumors, 28 normal colorectal tissues, and 5 normal liver tissues by immunohistochemistry. We also examined mRNA levels of the enzyme core 2 beta1,6-N-acetylglucosaminyltransferase (C2GnT1) in 20 well, 15 moderately, and 2 poorly differentiated colorectal adenocarcinomas, and in 5 normal colorectal tissues by using quantitative real-time polymerase chain reactions (RT-PCR). RESULTS: We observed high reactivity with CHO-131 mAb in approximately 70% of colorectal carcinomas and 87% of metastatic liver tumors but a lack of reactivity in colorectal adenomas and normal colonic and liver tissues. Positive reactivity with CHO-131 mAb was very prominent in neoplastic colorectal glands of well to moderately differentiated adenocarcinomas. The most intense staining with CHO-131 mAb was observed at the advancing edge of tumors with the deepest invasive components.Finally, we analyzed C2GnT1 mRNA levels in 37 colorectal adenocarcinomas and 5 normal colorectal tissues by RT-PCR. Significantly, we observed a greater than 15-fold increase in C2GnT1 mRNA levels in colorectal adenocarcinomas compared to normal colorectal tissues. CONCLUSION: C2-O-sLex, detected by the CHO-131 mAb, is a tumor associated antigen whose expression is highly upregulated in colorectal adenocarcinomas and metastatic liver tumors compared to normal tissues. C2-O-sLex is a potentially useful early predictor of metastasis.

A scoping review of opioid misuse in the rural United States.

INTRODUCTION: This study is a scoping review of the original research literature onthe misuse of opioids in the rural United States (US) and maps theliterature of interest to address the question: What does theoriginal research evidence reveal about the misuse of opioids inrural US communities? METHODS: This study used a modified preferred reporting items for systematicreviews and meta-analyses (PRISMA) approach which is organized byfive distinct elements or steps: beginning with a clearly formulatedquestion, using the question to develop clear inclusion criteria toidentify relevant studies, using an approach to appraise the studiesor a subset of the studies, summarizing the evidence using anexplicit methodology, and interpreting the findings of the review. RESULTS: The initial search yielded 119 peer reviewed articles and aftercoding, 41 papers met the inclusion criteria. Researcher generatedsurveys constituted the most frequent source of data. Most studieshad a significant quantitative dimension to them. All the studieswere observational or cross-sectional by design. CONCLUSIONS: This analysis found an emerging research literature that hasgenerated evidence supporting the claim that rural US residents andcommunities suffer a disproportionate burden from the misuseof opioidscompared to their urban or metropolitan counterparts.