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To examine the hypothesis that longer distance from home-to-hospital is associated with worse outcomes among hospitalizations for community-acquired sepsis.A secondary analysis of data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) prospective cohort of 30,239 white and Black US adults greater than or equal to 45 years old was conducted. Self-reported hospitalizations for serious infection between 2003 and 2012 fulfilling 2/4 systemic inflammatory response syndrome criteria were included. Estimated driving distance was derived from geocoded data and evaluated continuously and as quartiles of very close, close, far, very far (3.1, 3.1-5.8, 5.9-11.5, and11.5 miles respectively). The primary outcome was 30-day mortality while the secondary outcome was sequential organ failure assessment (SOFA) score on arrival.Of the 912 hospitalizations for community-acquired sepsis had adequate data for analysis. The median (interquartile range) estimated driving distance was 5.8 miles (3.1,11.7), and 54 (5.9%) experienced the primary outcome. Compared to living very close, participants living very far had a mortality odds ratio of 1.30 (95% CI 0.64,2.62) and presenting SOFA score difference of 0.33 (95% CI -0.03,0.68).Among a national sample of community-acquired sepsis hospitalizations, there was no significant association between home-to-hospital distance and either 30-day mortality or SOFA score on hospital presentation.

Background Although specific interventions previously demonstrated benefit in patients with ARDS, use of these interventions is inconsistent, and patient mortality remains high. The impact of variability in center management practices on ARDS mortality rates remains unknown. Research Question What is the impact of treatment variability on mortality in patients with moderate to severe ARDS in the United States? Study Design and Methods We conducted a multicenter, observational cohort study of mechanically ventilated adults with ARDS and Pa o 2 to F io 2 ratio of ≤ 150 with positive end-expiratory pressure of ≥ 5 cm H2O, who were admitted to 29 US centers between October 1, 2016, and April 30, 2017. The primary outcome was 28-day in-hospital mortality. Center variation in ventilator management, adjunctive therapy use, and mortality also were assessed. Results A total of 2,466 patients were enrolled. Median baseline Pa o 2 to F io 2 ratio was 105 (interquartile range, 78.0-129.0). In-hospital 28-day mortality was 40.7%. Initial adherence to lung protective ventilation (LPV; tidal volume, ≤ 6.5 mL/kg predicted body weight; plateau pressure, or when unavailable, peak inspiratory pressure, ≤ 30 mm H2O) was 31.4% and varied between centers (0%-65%), as did rates of adjunctive therapy use (27.1%-96.4%), methods used (neuromuscular blockade, prone positioning, systemic steroids, pulmonary vasodilators, and extracorporeal support), and mortality (16.7%-73.3%). Center standardized mortality ratios (SMRs), calculated using baseline patient-level characteristics to derive expected mortality rate, ranged from 0.33 to 1.98. Of the treatment-level factors explored, only center adherence to early LPV was correlated with SMR. Interpretation Substantial center-to-center variability exists in ARDS management, suggesting that further opportunities for improving ARDS outcomes exist. Early adherence to LPV was associated with lower center mortality and may be a surrogate for overall quality of care processes. Future collaboration is needed to identify additional treatment-level factors influencing center-level outcomes. Trial Registry ClinicalTrials.gov; No.: NCT03021824; URL: www.clinicaltrials.gov

Summary Background Sepsis is life-threatening organ dysfunction due to a dysregulated host response to infection. It is considered a major cause of health loss, but data for the global burden of sepsis are limited. As a syndrome caused by underlying infection, sepsis is not part of standard Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimates. Accurate estimates are important to inform and monitor health policy interventions, allocation of resources, and clinical treatment initiatives. We estimated the global, regional, and national incidence of sepsis and mortality from this disorder using data from GBD 2017. Methods We used multiple cause-of-death data from 109 million individual death records to calculate mortality related to sepsis among each of the 282 underlying causes of death in GBD 2017. The percentage of sepsis-related deaths by underlying GBD cause in each location worldwide was modelled using mixed-effects linear regression. Sepsis-related mortality for each age group, sex, location, GBD cause, and year (1990–2017) was estimated by applying modelled cause-specific fractions to GBD 2017 cause-of-death estimates. We used data for 8·7 million individual hospital records to calculate in-hospital sepsis-associated case-fatality, stratified by underlying GBD cause. In-hospital sepsis-associated case-fatality was modelled for each location using linear regression, and sepsis incidence was estimated by applying modelled case-fatality to sepsis-related mortality estimates. Findings In 2017, an estimated 48·9 million (95% uncertainty interval [UI] 38·9–62·9) incident cases of sepsis were recorded worldwide and 11·0 million (10·1–12·0) sepsis-related deaths were reported, representing 19·7% (18·2–21·4) of all global deaths. Age-standardised sepsis incidence fell by 37·0% (95% UI 11·8–54·5) and mortality decreased by 52·8% (47·7–57·5) from 1990 to 2017. Sepsis incidence and mortality varied substantially across regions, with the highest burden in sub-Saharan Africa, Oceania, south Asia, east Asia, and southeast Asia. Interpretation Despite declining age-standardised incidence and mortality, sepsis remains a major cause of health loss worldwide and has an especially high health-related burden in sub-Saharan Africa. Funding The Bill & Melinda Gates Foundation, the National Institutes of Health, the University of Pittsburgh, the British Columbia Children's Hospital Foundation, the Wellcome Trust, and the Fleming Fund.

Guidelines recommend crystalloids for fluid resuscitation in sepsis/shock and switching to albumin in cases where crystalloids are insufficient. We evaluated hemodynamic response to crystalloids/colloids in critically ill adults.The primary research question was: "Are crystalloids sufficient for volume replacement in severe indications (intensive care unit [ICU]/critical illness)?" Randomized, controlled trials (RCTs) were identified using PubMed and EMBASE, and screened against predefined inclusion/exclusion criteria. Meta-analyses were performed on extracted data.Fifty-five RCTs (N = 27,036 patients) were eligible. Central venous pressure was significantly lower with crystalloids than with albumin, hydroxyethyl starch (HES), or gelatin (all p .001). Mean arterial pressure was significantly lower with crystalloids vs. albumin (mean difference [MD]: -3.5 mm Hg; p = .03) or gelatin (MD: -9.2 mm Hg; p = .02). Significantly higher volumes of crystalloids were administered vs. HES (MD: +1775 mL); volume administered was numerically higher vs. albumin (MD: +1985 mL). Compared with the albumin group, cardiac index was significantly lower in the crystalloid group (MD: -0.6 L/min/mCrystalloids were less efficient than colloids at stabilizing resuscitation endpoints; guidance on when to switch is urgently required.

As the emergence of SARS-CoV-2 variants brings the global pandemic to new levels, the performance of current rapid antigen tests against variants of concern and interest (VOC/I) is of significant public health concern. Here, we report assessment of the Abbot BinaxNOW COVID-19 Antigen Self-Test. Using genetically sequenced remnant clinical samples collected from individuals positive for SARS-CoV-2, we assessed the performance of BinaxNOW against the variants that currently pose public health threats. We measured the limit of detection of BinaxNOW against various VOC/I in a blinded manner. BinaxNOW successfully detected the Omicron (B.1.1.529), Mu (B.1.621), Delta (B.1.617.2), Lambda (C.37), Gamma (P.1), Alpha (B.1.1.7), Beta (B.1.351), Eta (B.1.525), and P.2 variants and at low viral concentrations. BinaxNOW also detected the Omicron variant in individual remnant clinical samples. Overall, these data indicate that this inexpensive and simple-to-use, FDA-authorized and broadly distributed rapid test can reliably detect Omicron, Delta, and other VOC/I.

Background: Prompt antibiotic administration improves outcomes, but antibiotic administration prior to culture collection cultures can decrease culture yield. We sought to determine impact of antibiotic administration timing on the positivity rate of blood, urine, and respiratory cultures. Methods: Over three years we conducted a multicenter retrospective cohort study of adult inpatients with blood, urine or respiratory cultures collected who received at least one antibiotic. The first specimen of each culture type was included. The primary outcomes were rates of positive cultures and time of collection relative to first antibiotic administration. Findings: Of 34,677 patients with at least one blood, urine or respiratory culture collected in addition to at least one antibiotic dose administered during the study period, 14,909 cultures (7,351 sets of blood, 7,081 urine, and 477 respiratory cultures) were eligible for analysis. Most (79%) cultures were collected before antibiotic initiation. During the first hour following antibiotic initiation, blood culture positivity decreased by 18% for every 15 minutes (odds ratio [OR]: 0·82, 95% confidence interval [CI]: 0·71-0·95), urine culture positivity decreased by 19% for every 15 minutes (OR: 0·81 [95% CI: 0·76-0·86]) there was no significant change in respiratory culture positivity. Interpretation: Antibiotic administration significantly and promptly decreases yield of blood and urine bacterial cultures. Funding Statement: JTJ was partly supported by the CDC Prevention Epicenters (U01CK00054). Declaration of Interests: The authors have no conflict of interest. Ethics Approval Statement: The study was reviewed and considered exempt by the Emory University’s Institutional Review Board.

Background: A significant proportion of adults have normal weight obesity (NWO), defined as a normal body mass index (BMI) but disproportionately high body fat percentage. Individuals with NWO may have increased risk of cardiometabolic disorders and lower exercise tolerance, but it is unclear if this obesity phenotype is linked with dysregulated production of adipokines or myokines such as adiponectin and apelin, respectively. Methods: This cross-sectional, secondary analysis included 177 working adults (mean age 49.6 ± 9.9 yrs, 64% female). Plasma high-molecular weight adiponectin and apelin levels were measured by ELISA. Body composition and fat distribution were assessed using dual energy X-ray absorptiometry. Exercise tolerance (VO2 maximum) was determined by treadmill testing. NWO was defined as a BMI 30% for women or >23% for men. Participants were categorized as lean, NWO, or overweight-obese. Results: A total of 14.7% of subjects were categorized as lean, 23.7% as having NWO, and 61.6% as having overweight-obesity. Plasma adiponectin levels were elevated in the overweight-obesity group (P 0.05). Adiponectin concentrations were inversely associated with BMI, fat mass, fat mass percent, visceral fat, and trunk to leg fat ratio and positively associated with leg fat mass (all P

Electronic health records (EHR) with computerized physician order entry have become exceedingly common and government incentives have urged implementation. The purpose of this study was to ascertain the effect of EHR implementation on medical intensive care unit (MICU) mortality, length of stay (LOS), hospital LOS and medication errors.Prospective, observational study from July 2010-June 2011 in MICU at an urban teaching hospital in Atlanta, Georgia of 797 patients admitted to the MICU; 281 patients before the EHR implementation and 516 patients post-EHR implementation.Compared with the preimplementation period (N = 43 per 281), the mortality risk at 4 months post-EHR implementation (N = 41 per 247) and at 8 months post-EHR implementation (N = 26 per 269) significantly decreased (P0.001). In addition, the mean MICU LOS statistically decreased from 4.03 ± 1.06 days pre-EHR to 3.26 ± 1.06 days 4 months post-EHR and to 3.12 ± 1.05 days 8 months post-EHR (P = 0.002). However, the mean hospital LOS was not statistically decreased. Although medication errors increased after implementation (P = 0.002), this was attributable to less severe errors and there was actually a decrease in the number of severe medication errors (both P0.001).We report a survival benefit following the implementation of EHR with computerized physician order entry in a critical care setting and a concomitant decrease in the number of severe medication errors. Although overall hospital LOS was not shortened, this study proposes that EHR implementation in a busy urban hospital was associated with improved ICU outcomes.

Somatic mutation in neurons is linked to neurologic disease and implicated in cell type diversification. However, the origin, extent and patterns of genomic mutation in neurons remain unknown. We established a nuclear transfer method to clonally amplify the genomes of neurons from adult mice for whole genome sequencing. Comprehensive mutation detection and independent validation revealed that individual neurons harbor ~100 unique mutations from all classes, but lack recurrent rearrangements. Most neurons contain at least one gene disrupting mutation and rare (0-2) mobile element insertions. The frequency and gene bias of neuronal mutations differs from other lineages, potentially due to novel mechanisms governing post-mitotic mutation. Fertile mice were cloned from several neurons, establishing the compatibility of mutated adult neuronal genomes with reprogramming to pluripotency and development.

We determined the prevalence of risk factors for the development of acute respiratory distress syndrome (ARDS), outcomes of critical illness, and the impact of highly active antiretroviral therapy in HIV-1-infected patients. We hypothesized that in an urban county hospital, HIV-1-infected patients with ARDS would have a higher mortality than their HIV-1-uninfected counterparts.Subjects were enrolled between 2006 and 2012. Baseline patient demographics, comorbidities, illness severity, causes of ARDS, and clinical outcomes were obtained. The primary end point was hospital mortality.A total of 178 subjects with ARDS were enrolled in the study; 40 (22%) were infected with HIV-1. The median CD4 count was 75 (15.3-198.3), and 25% were on highly active antiretroviral therapy. HIV-1-infected subjects were significantly younger (44 vs 52 years; P.01) and had higher rates of asthma, chronic obstructive pulmonary disease, pneumonia, history of hospital-acquired infections, and prior sepsis. HIV-1-infected subjects had greater illness severity by Acute Physiology and Chronic Health Evaluation II scores (29 [24-31] vs 24 [22-25]; P.01). Hospital mortality was not higher among HIV-1-infected subjects compared with HIV-1-uninfected subjects (50.0% vs 38.4%; P = .19).In patients with ARDS, HIV-1 infection was associated with greater illness severity but was not associated with higher mortality in ARDS. Future studies need to be done to evaluate the factors that contribute to high morbidity and mortality in medically vulnerable populations who develop ARDS.

Objective Bronchoscopy and bronchoalveolar lavage (BAL) are common procedures in intensive care units; however, no contemporaneous safety and outcomes data have been reported, particularly for critically ill patients. Design This is a retrospective analysis of prospectively collected data from teaching hospital adult intensive care units. Interventions One hundred mechanically ventilated patients with severe sepsis, septic shock, acute lung injury (ALI), and/or acute respiratory distress syndrome underwent bronchoscopy with unilateral BAL. Data collected included demographics, presence of sepsis or ALI, Pa o 2 to F io 2 ratio, positive end-expiratory pressure, Acute Physiology and Chronic Health Evaluation score, Sequential Organ Failure Assessment score, and peri- or postprocedural complications. Results Men comprised 51% of the patients; 81% of the patients were black, and 15% were white. The mean age was 52 (SD, ± 16) years. The mean Acute Physiology and Chronic Health Evaluation score was 22 (± 7.5), whereas the median Sequential Organ Failure Assessment score was 9 (interquartile range, 5-12). Ten patients (10%) had complications during or immediately after the procedure. Hypoxemia during or immediately after the BAL was the most common complication. Ninety percent of the complications were related to transient hypoxemia, whereas bradycardia and hypotension each occurred in 1 patient. Age, female sex, and higher positive end-expiratory pressure were associated with complications. Conclusions Bronchoscopy with BAL in critically ill patients with sepsis and ALI is well tolerated with low risk of complications, primarily related to manageable hypoxemia.

Psychological stress triggers a cascade of physiologic responses including activation of the hypothalamic-pituitary axis and increase in adrenocorticotropic hormones. This contributes to an imbalance between the sympathetic and parasympathetic nervous systems, and can stimulate oxidant stress and

Background Sepsis is a major public health problem. Social factors may affect health behaviors, economic resources, and immune response, leading to hospitalization for infection. This study examines the association between marital status and sepsis incidence and outcomes in a population-based cohort. Methods We analyzed 1,113,581 hospitalizations in New Jersey in 2006. We estimated risk-adjusted incidence rate ratios (IRRs) for sepsis among divorced, widowed, legally separated, single, and married subjects using population data from the American Community Survey. We used multivariable logistic regression to estimate marital status-specific hospital mortality. Results We identified 37,524 hospitalizations for sepsis, of which 40% were among married (14,924), 7% were among divorced (2,548), 26% were among widowed (9,934), 2% (763) were among legally separated, and 26% (9355) were among single subjects. The incidence of hospitalization for sepsis was 5.8 per 1,000 population. The age, sex, and race-adjusted IRR for hospitalization with sepsis was greatest for single (IRR = 3.47; 95% CI, 3.1, 3.9), widowed (IRR = 1.38; 95% CI, 1.2, 1.6), and legally separated (IRR = 1.46; 95% CI, 1.2, 1.8) subjects compared with married (referent). We observed that single men and women and divorced men had greater odds of in-hospital mortality compared with married men; widowed and legally separated men and all ever-married women had no excess mortality during hospitalization for sepsis. Conclusions Hospitalization for sepsis is more common among single, widowed, and legally separated individuals, independent of other demographic factors. Among patients hospitalized for sepsis, single and divorced men and single women experience greater hospital mortality, highlighting the need to characterize the potentially modifiable mechanisms linking marital status to its greater burden of critical illness.

BACKGROUND: Truncal obesity is associated with metabolic syndrome and cardiovascular risk. Although vascular health is influenced by weight, it is not known whether changes in fat distribution modulate arterial function. OBJECTIVE: We assessed how changes in truncal (android) fat at one year affect arterial stiffness and endothelial function. METHODS: We recruited 711 healthy volunteers (235 males, age 48±11) into the Emory Predictive Health Study; 498 returned at one year. Measurements included anthropometric and chemistry panels, fat mass using dual-energy X-ray absorptiometry, arterial stiffness indices [pulse wave velocity (PWV), augmentation index (AIx), and subendocardial viability ratio (SEVR)] (Sphygmocor), flow-mediated dilation (FMD) and reactive hyperemia index (RHI, Endo-PAT). RESULTS: At baseline, measures of body mass correlated with PWV, AIx, SEVR, and FMD. A multivariable analysis including body mass index (BMI) and traditional risk factors, BMI remained an independent predictor of PWV, AIx, SEVR, and FMD. In a model including BMI and measures of fat distribution, android fat remained an independent predictor of PWV (β= .31, p= .004), AIx (β = .24, p= .008), and SEVR (β = −.41, p

Study objectives To evaluate the longitudinal epidemiology of sepsis in patients with a history of cancer and to specifically examine sepsis-related disparities in risk or outcome. Design Sepsis cases from 1979 through 2001 using a nationally representative sample of nonfederal acute-care hospitalizations in the United States (the National Hospital Discharge Survey) integrated with cancer prevalence from the Surveillance, Epidemiology, and End Results database. Setting Eight hundred fifty-four million acute-care hospitalizations and 8.9 million patients with cancer. Patients or participants Patients with a history of cancer hospitalized with a diagnosis of sepsis. Measurements and results From 1979 to 2001, there were a total of 1,781,445 cases of sepsis in patients with cancer, yielding a mean annual incidence rate of 1,465 cases per 100,000 cancer patients and a relative risk [RR] of 9.77 compared to noncancer patients (95% confidence interval [95% CI], 9.67 to 9.88). In contrast to the absolute number of cases, the incidence rate of sepsis decreased over time, from a peak of 1,959 cases per 100,000 cancer patients in 1987 to 995 cases per 100,000 in 2001. The distribution of infectious sources causing sepsis was associated with the type of malignancy. White cancer patients had a lower risk for sepsis compared to nonwhites (African-American RR, 1.28; 95% CI, 1.16 to 1.40) and other races (RR, 1.47; 95% CI, 1.22 to 1.72); and male cancer patients had a higher risk for sepsis compared to female cancer patients (male RR, 1.17; 95% CI, 1.10 to 1.23). Cancer was an independent predictor of death among sepsis patients by multivariable analysis (adjusted odds ratio for death, 1.98; 95% CI, 1.97 to 1.99). Conclusions Patients with a history of cancer are at increased risk for acquiring and subsequently dying from sepsis, compared to the general population, although incidence and fatality rates are decreasing over time. There are significant racial and gender disparities in the incidence and outcome of sepsis among cancer patients that require explanation.

Background: Obesity is a pro-inflammatory state leading to endothelial cell injury and dysfunction. In particular, central (android) obesity is associated with increased cardiovascular disease risk. Bone marrow derived CD34+ progenitor cells (PC) levels are elevated in patients with high body mass

The role of 1,25-dihydroxy-vitamin D3 (VitD3) in cardiovascular disease remains controversial. Vitamin D receptors on progenitor cells (PCs) promote maturation and vascular repair by inducing SDF1 expression and homing of CXCR4+ angiogenic myeloid cells. Whether VitD3 levels modulate circulating PCs

Current goals of healthcare delivery extend beyond treating and preventing disease outcomes to improvement in the quality of life. Clinicians routinely utilize patients' subjective reports of functional well-being and physical capacity to evaluate cardiopulmonary fitness, screen for illness-related impact on daily activities and to ascertain effectiveness of therapy. Similarly, standardized questionnaires assessing self-perceived physical and functional health are employed as clinical end-points and are also used to compare effectiveness of diagnostic and therapeutic modalities [1]. While there is no established gold standard for assessment of perceived health and well-being, the Short Form-36 version 2 Health Survey (SF-36) performs reliably in several clinical settings and across many patient populations [2]. The SF-36 allows for separate assessment of physical and mental health functioning, summarized by the physical (PCS) and mental (MCS) component summary scores, respectively. The internal consistency of SF-36 has been validated to represent an accurate portrayal of a responder's quality of life, as well as the clinician's interpretation of patients' health [3]. The SF-36 predicts morbidity and mortality in the general population, and lower PCS scores forecast dismal outcomes in patients with cardiovascular disease (CVD) [3]. However, its utility as a predictor of subclinical vascular disease has not been investigated previously [4]. Measures of arterial wall thickness and stiffness are powerful predictors of both future incidence of hypertension in asymptomatic individuals, as well as adverse outcomes in at-risk patient populations [5]. We examined the relationship between the physical (PCS) and mental (MCS) component summary scores of the SF-36 and subclinical vascular disease in subjects free of cardiovascular disease, with the hypothesis that low scores will be associated with vascular disease and dysfunction. We examined PCS and MCS scores in 609 University employees without overt CVD (Table 1), who underwent comprehensive evaluation of vascular structure and function, including carotid artery intima-media thickness (IMT) and arterial stiffness measured as PWV, central augmentation index (AIX), and subendocardial viability ratio (SEVR). The PCS score correlated negatively with age (r =−0.09, p = 0.027), body mass index (BMI; r = −0.28, p b 0.001) and the Framingham Risk Score (FRS; r = −0.12, p = 0.003), indicating higher scores in younger, leaner subjects with lower risk factor burden. PCS scores were also lower in women, African Americans, and in subjects with diabetes, hypertension, hyperlipidemia or smoking (Table 2). Lower PCS scores were associated with worse arterial stiffness, indicated by higher PWV and AIX, and lower SEVR (r = −0.14, −0.15 and 0.2, respectively; p ≤ 0.001 for all); as well as increased carotid IMT (r = −0.18, p ≤ 0.001) (Fig. 1). Following adjustment for FRS, BMI and race, the PCS, but not the MCS score remained independently associated with PWV (β = −0.13, p b 0.001), AIX (β = −0.1, p = 0.008), SEVR (β = 0.22, p b 0.001) and IMT (β = −0.12, p = 0.001). Each 5-point incrementin the PCS score is associated with 0.1 m/s and 0.01 mm change in PWV and IMT, respectively. Three questions in the SF-36 had significant univariate associations with all vascular measures; including IMT, PWV, AIX and SEVR (p-ANOVA b 0.03 for all questions). These were whether the subject's “health” status limits common daily activities such as: 1 — vigorous activities; 2 — bending, kneeling, or stooping and 3 — walking more than 1 mile. In conclusion, poor self-reported physical and functional health measured with the PCS score is associated with arterial stiffness and vascular dysfunction, irrespective of concomitant risk burden in this large multiethnic population with a relatively low risk factor