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BackgroundAlthough anemia is common in patients with myocardial infarction (MI), management remains controversial. We quantified the association of anemia with in-hospital outcomes and resource utilization in patients admitted with MI using a large national database.MethodsAll hospitalizations with a primary diagnosis code for acute MI in the National Inpatient Sample (NIS) between 2014 and 2018 were identified. Among these hospitalizations, patients with anemia were identified using a secondary diagnosis code. Data on demographic and clinical variables were collected. Outcomes of interest included in-hospital adverse events, length of stay (LOS), and total cost. Multivariable logistic regression and generalized linear models were used to evaluate the relationship between anemia and outcomes.ResultsAmong 1,113,181 MI hospitalizations, 254,816 (22.8%) included concomitant anemia. Anemic patients were older and more likely to be women. After adjustment for demographics and comorbidities, anemia was associated with higher mortality (7.1 vs. 4.3%; odds ratio 1.09; 95% confidence interval [CI] 1.07-1.12, pConclusionIn MI patients, anemia was associated with higher in-hospital mortality, adverse events, total cost, and length of stay. Transfusion was associated with increased mortality, and its role in MI requires further research.

Severe anemia is commonly treated with red blood cell transfusion. Clinical trials have demonstrated that a restrictive transfusion strategy of 7-8 g/dL is as safe as a liberal transfusion strategy of 9-10 g/dL in many clinical settings. Evidence is lacking for subgroups of patients, including those with pre-existing coronary artery disease, acute myocardial infarction, congestive heart failure, and myelodysplastic neoplasms. We present three clinical vignettes that highlight the clinical challenges in caring for patients with coronary artery disease with gastrointestinal bleeding, congestive heart failure, and myelodysplastic neoplasms. We emphasize that transfusion practice should be guided by patient symptoms and preferences in conjunction with the hemoglobin concentration. Along with the transfusion decision, evaluation, and management of the etiology of the anemia is essential. Iron-restricted erythropoiesis is a common cause of anemia severe enough to be considered for red blood cell transfusion but diagnosis and management of absolute iron deficiency anemia, the anemia of inflammation with functional iron deficiency, or their combination may be problematic. Intravenous iron therapy is generally the treatment of choice for absolute iron deficiency in patients with complex medical disorders, with or without coexisting functional iron deficiency.

Accumulating evidence from clinical trials suggests that a lower (restrictive) hemoglobin threshold (8% g/dL) for red blood cell (RBC) transfusion, compared with a higher (liberal) threshold (≥10 g/dL) is safe. However, in anemic patients with acute myocardial infarction (MI), maintaining a higher hemoglobin level may increase oxygen delivery to vulnerable myocardium resulting in improved clinical outcomes. Conversely, RBC transfusion may result in increased blood viscosity, vascular inflammation, and reduction in available nitric oxide resulting in worse clinical outcomes. We hypothesize that a liberal transfusion strategy would improve clinical outcomes as compared to a more restrictive strategy.We will enroll 3500 patients with acute MI (type 1, 2, 4b or 4c) as defined by the Third Universal Definition of MI and a hemoglobin10 g/dL at 144 centers in the United States, Canada, France, Brazil, New Zealand, and Australia. We randomly assign trial participants to a liberal or restrictive transfusion strategy. Participants assigned to the liberal strategy receive transfusion of RBCs sufficient to raise their hemoglobin to at least 10 g/dL. Participants assigned to the restrictive strategy are permitted to receive transfusion of RBCs if the hemoglobin falls below 8 g/dL or for persistent angina despite medical therapy. We will contact each participant at 30 days to assess clinical outcomes and at 180 days to ascertain vital status. The primary endpoint is a composite of all-cause death or recurrent MI through 30 days following randomization. Secondary endpoints include all-cause mortality at 30 days, recurrent adjudicated MI, and the composite outcome of all-cause mortality, nonfatal recurrent MI, ischemia driven unscheduled coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting), or readmission to the hospital for ischemic cardiac diagnosis within 30 days. The trial will assess multiple tertiary endpoints.The MINT trial will inform RBC transfusion practice in patients with acute MI.

The REGAIN (Regional versus General Anesthesia for Promoting Independence after Hip Fracture) trial found similar ambulation and survival at 60 days with spinal versus general anesthesia for hip fracture surgery. Trial outcomes evaluating pain, prescription analgesic use, and patient satisfaction have not yet been reported.To compare pain, analgesic use, and satisfaction after hip fracture surgery with spinal versus general anesthesia.Preplanned secondary analysis of a pragmatic randomized trial. (ClinicalTrials.gov: NCT02507505).46 U.S. and Canadian hospitals.Patients aged 50 years or older undergoing hip fracture surgery.Spinal or general anesthesia.Pain on postoperative days 1 through 3; 60-, 180-, and 365-day pain and prescription analgesic use; and satisfaction with care.A total of 1600 patients were enrolled. The average age was 78 years, and 77% were women. A total of 73.5% (1050 of 1428) of patients reported severe pain during the first 24 hours after surgery. Worst pain over the first 24 hours after surgery was greater with spinal anesthesia (rated from 0 [no pain] to 10 [worst pain imaginable]; mean difference, 0.40 [95% CI, 0.12 to 0.68]). Pain did not differ across groups at other time points. Prescription analgesic use at 60 days occurred in 25% (141 of 563) and 18.8% (108 of 574) of patients assigned to spinal and general anesthesia, respectively (relative risk, 1.33 [CI, 1.06 to 1.65]). Satisfaction was similar across groups.Missing outcome data and multiple outcomes assessed.Severe pain is common after hip fracture. Spinal anesthesia was associated with more pain in the first 24 hours after surgery and more prescription analgesic use at 60 days compared with general anesthesia.Patient-Centered Outcomes Research Institute

Background We report faculty affairs lessons from the formation and academic restructuring of Rutgers Biomedical and Health Sciences. Our approach may be a blueprint for development of a new track system that can be adapted by other institutions, after consideration of their own special circumstances. Methods We created new Appointments and Promotions guidelines consisting of one Tenure Track and four Non-Tenure Tracks, each with different missions. We restructured faculty performance evaluations to include mission-based criteria, an expanded rating scale, and specific expectations. After negotiating these new processes with our faculty union, we enacted central oversight to ensure uniform application of these processes and their associated criteria. We communicated the guidelines and the evaluation system widely. We created programs for universal mentoring, publishing education, diversity, and faculty development. Results All faculty in our seven schools went through track selection. Anxiety and incomplete understanding improved after implementation. Evaluations with expectations for the following year and an expanded scale for more nuanced assessment served as mentoring tools. Requirements for mentor assignments and diversity education created an atmosphere of nurturing and inclusion. Publications, extramural support, and faculty satisfaction increased after implementation of the guidelines. Conclusion Lessons included the need to review and learn from guidelines at other institutions, to create tracks that align with different jobs, the necessity for central oversight for uniform application of criteria, the need for extensive and frequent communication with faculty, and that fear of change is only reduced after evidence of success of a new structure. The most important lesson was that faculty rise to expectations when clear, ambitious criteria are delineated and universally applied.

BACKGROUND: Hip fractures are associated with a high rate of morbidity and mortality, and successful ambulation after surgery is an important outcome in this patient population. OBJECTIVE: This study aims to determine whether 25-hydroxyvitamin D [25(OH)D] concentration or the Geriatric Nutritional Risk Index (GNRI) is associated with mortality or rates of walking in a patient cohort after hip fracture surgery. METHODS: Patients undergoing hip fracture repair from a multisite study in North America were included. Mortality and mobility were assessed at 30 and 60 d after surgery. Serum albumin, 25(OH)D, and intact parathyroid hormone were measured. Patients were characterized according to 25(OH)D

The risks for anaphylaxis among intravenous (IV) iron products currently in use have not been assessed.To compare risks for anaphylaxis among 5 IV iron products that are used frequently.Retrospective cohort study using a target trial emulation framework.Medicare fee-for-service data with Part D coverage between July 2013 and December 2018.Older adults receiving their first administration of IV iron.The primary outcome was the occurrence of anaphylaxis within 1 day of IV iron administration, ascertained using a validated case definition. Analysis was adjusted for 40 baseline covariates using inverse probability of treatment weighting. The adjusted incidence rates (IRs) for anaphylaxis per 10 000 first administrations and odds ratios (ORs) were computed.The adjusted IRs for anaphylaxis per 10 000 first administrations were 9.8 cases (95% CI, 6.2 to 15.3 cases) for iron dextran, 4.0 cases (CI, 2.5 to 6.6 cases) for ferumoxytol, 1.5 cases (CI, 0.3 to 6.6 cases) for ferric gluconate, 1.2 cases (CI, 0.6 to 2.5 cases) for iron sucrose, and 0.8 cases (CI, 0.3 to 2.6 cases) for ferric carboxymaltose. Using iron sucrose as the referent category, the adjusted ORs for anaphylaxis were 8.3 (CI, 3.5 to 19.8) for iron dextran and 3.4 (CI, 1.4 to 8.3) for ferumoxytol. When cohort entry was restricted to the period after withdrawal of high-molecular-weight iron dextran from the U.S. market in 2014, the risk for anaphylaxis associated with low-molecular-weight iron dextran (OR, 8.4 [CI, 2.8 to 24.7]) did not change appreciably. Anaphylactic reactions requiring hospitalizations were observed only among patients using iron dextran or ferumoxytol.Generalizability to non-Medicare populations.The rates of anaphylaxis were very low with all IV iron products but were 3- to 8-fold greater for iron dextran and ferumoxytol than for iron sucrose.None.

The effects of spinal anesthesia as compared with general anesthesia on the ability to walk in older adults undergoing surgery for hip fracture have not been well studied.We conducted a pragmatic, randomized superiority trial to evaluate spinal anesthesia as compared with general anesthesia in previously ambulatory patients 50 years of age or older who were undergoing surgery for hip fracture at 46 U.S. and Canadian hospitals. Patients were randomly assigned in a 1:1 ratio to receive spinal or general anesthesia. The primary outcome was a composite of death or an inability to walk approximately 10 ft (3 m) independently or with a walker or cane at 60 days after randomization. Secondary outcomes included death within 60 days, delirium, time to discharge, and ambulation at 60 days.A total of 1600 patients were enrolled; 795 were assigned to receive spinal anesthesia and 805 to receive general anesthesia. The mean age was 78 years, and 67.0% of the patients were women. A total of 666 patients (83.8%) assigned to spinal anesthesia and 769 patients (95.5%) assigned to general anesthesia received their assigned anesthesia. Among patients in the modified intention-to-treat population for whom data were available, the composite primary outcome occurred in 132 of 712 patients (18.5%) in the spinal anesthesia group and 132 of 733 (18.0%) in the general anesthesia group (relative risk, 1.03; 95% confidence interval [CI], 0.84 to 1.27; P = 0.83). An inability to walk independently at 60 days was reported in 104 of 684 patients (15.2%) and 101 of 702 patients (14.4%), respectively (relative risk, 1.06; 95% CI, 0.82 to 1.36), and death within 60 days occurred in 30 of 768 (3.9%) and 32 of 784 (4.1%), respectively (relative risk, 0.97; 95% CI, 0.59 to 1.57). Delirium occurred in 130 of 633 patients (20.5%) in the spinal anesthesia group and in 124 of 629 (19.7%) in the general anesthesia group (relative risk, 1.04; 95% CI, 0.84 to 1.30).Spinal anesthesia for hip-fracture surgery in older adults was not superior to general anesthesia with respect to survival and recovery of ambulation at 60 days. The incidence of postoperative delirium was similar with the two types of anesthesia. (Funded by the Patient-Centered Outcomes Research Institute; REGAIN ClinicalTrials.gov number, NCT02507505.).

BACKGROUND The number of red blood cell units transfused per capita in China is lower than in western countries and the reason(s) for the difference is unknown. STUDY DESIGN AND METHODS We randomly chose 5050 transfused patients from five Chinese hospitals. We compared transfused cases to nontransfused controls matched for the same underlying diagnosis. We assessed the pretransfusion hemoglobin (Hb) trigger and other clinical characteristics associated with transfusion. After stratifying by underlying disease, we compared pretransfusion Hb level in Chinese hospitals to 12 US hospitals. RESULTS In 5050 patients who received transfusion, the pretransfusion Hb levels were lower in medical (6.3 g/dL) compared to surgical patients receiving transfusion postoperatively (8.1 g/dL). In patients with nonsurgical diagnoses, the pretransfusion Hb was much lower than that in the United States; the difference in mean Hb level varied by underlying diagnosis from 0.4 to 1.8 g/dL. In case-control analysis of cases (n = 1356) compared to controls (n = 1201), the pretransfusion Hb showed the strongest association with transfusion. Compared to 10 g/dL, the odds ratio (95% confidence interval) for pretransfusion Hb of 7 to 7.9 g/dL was 37.7 (24.8-57.4). CONCLUSION Transfusion triggers in five Chinese hospitals appear comparable to those in the United States for surgical patients; however, medical patients have lower pretransfusion Hb levels (approx. 6 g/dL). Of the factors assessed, the pretransfusion Hb was most strongly associated with transfusion. The clinical impact of lower transfusion thresholds used in China is unknown.

Monitoring the burden and spread of infection with the new coronavirus SARS-CoV-2, whether within small communities or in large geographical settings, is of paramount importance for public health purposes. Serology, which detects the host antibody response to the infection, is the most appropriate tool for this task, since virus-derived markers are most reliably detected during the acute phase of infection. Here we show that our ELISA protocol, which is based on antibody binding to the Receptor Binding Domain (RBD) of the S1 subunit of the viral Spike protein expressed as a novel fusion protein, detects antibody responses to SARS-CoV-2 infection and COVID-19 vaccination.We also show that our ELISA is accurate and versatile. It compares favorably with commercial assays widely used in clinical practice to determine exposure to SARS-CoV-2. Moreover, our protocol accommodates use of various blood- and non-blood-derived biospecimens, such as breast milk, as well as dried blood obtained with microsampling cartridges that are appropriate for remote collection. As a result, our RBD-based ELISA protocols are well suited for seroepidemiology and other large-scale studies requiring parsimonious sample collection outside of healthcare settings.

Background We studied risk factors, antibodies, and symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a diverse, ambulatory population. Methods A prospective cohort (n = 831) previously undiagnosed with SARS-CoV-2 infection underwent serial testing (SARS-CoV-2 polymerase chain reaction, immunoglobulin G [IgG]) for 6 months. Results Ninety-three participants (11.2%) tested SARS-CoV-2-positive: 14 (15.1%) asymptomatic, 24 (25.8%) severely symptomatic. Healthcare workers (n = 548) were more likely to become infected (14.2% vs 5.3%; adjusted odds ratio, 2.1; 95% confidence interval, 1.4–3.3) and severely symptomatic (29.5% vs 6.7%). IgG antibodies were detected after 79% of asymptomatic infections, 89% with mild-moderate symptoms, and 96% with severe symptoms. IgG trajectories after asymptomatic infections (slow increases) differed from symptomatic infections (early peaks within 2 months). Most participants (92%) had persistent IgG responses (median 171 days). In multivariable models, IgG titers were positively associated with symptom severity, certain comorbidities, and hospital work. Dyspnea and neurologic changes (including altered smell/taste) lasted ≥ 120 days in ≥ 10% of affected participants. Prolonged symptoms (frequently more severe) corresponded to higher antibody levels. Conclusions In a prospective, ethnically diverse cohort, symptom severity correlated with the magnitude and trajectory of IgG production. Symptoms frequently persisted for many months after infection. Clinical Trials Registration. NCT04336215.

BACKGROUND Plasma is frequently administered to patients with prolonged INR prior to invasive procedures. However, there is limited evidence evaluating efficacy and safety. STUDY DESIGN AND METHODS We performed a pilot trial in hospitalized patients with INR between 1.5 and 2.5 undergoing procedures conducted outside the operating room. We excluded patients undergoing procedures proximal to the central nervous system, platelet counts

Given the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the recent implementation of SARS-CoV-2 vaccination, we have much to learn about the duration of immune protection and the interface between the immune responses to infection and to vaccination. To address these questions, we monitored immune responses to SARS-CoV-2 infection in convalescent individuals over seven months and following mRNA vaccination. Spike Receptor-Binding-Domain (RBD)-specific circulating antibodies and plasma neutralizing activity generally decreased over time, whereas RBD-specific memory B cells persisted. Additionally, using antibody depletion techniques, we showed that the neutralizing activity of plasma specifically resides in the anti-RBD antibodies. More vigorous antibody and B cell responses to vaccination were observed in previously infected subjects relative to uninfected comparators, presumably due to immune priming by infection. SARS-CoV-2 infection also led to increased numbers of double negative B memory cells, which are described as a dysfunctional B cell subset. This effect was reversed by SARS-CoV-2 vaccination, providing a potential mechanistic explanation for the vaccination-induced reduction in symptoms in patients with "Long-COVID".

The role of advanced practice providers has expanded in the hospital setting. However, little data exist examining the impact of these providers. Our purpose was to determine the effect of adding nurse practitioners in a complementary role on the quality and efficiency of care of hospitalized patients. A retrospective cohort study evaluated adult patients admitted by private physicians (without house staff or non-physician providers) to a general medical-surgical unit in an academic medical center. The admissions department allocated patients as beds became available and nurse practitioners were assigned to patients until their caseload was reached. Outcomes included length of hospital stay, in-hospital mortality, admission costs, 30-day readmissions, transfer to a more intensive care level, and discharge order time. Of the 382 patients included in this study, 263 were assigned to the nurse practitioner group. Hospital mortality was lower in the nurse practitioner group [OR 0.11 (95% CI 0.02&ndash, 0.51)] as was transfer to more intensive care level [OR 0.39 (95% CI 0.20&ndash, 0.75)], however, the nurse practitioner group had longer length of stay (geometric mean = 5.80 days for nurse practitioners, 3.63 days for no nurse practitioners, p &lt, 0.0001) and higher cost per patient (geometric mean = USD 6631 vs. USD 5121, p = 0.005). The results were unchanged when models were adjusted for potential confounders. Adding nurse practitioners can yield improved clinical outcomes (lower hospital mortality and fewer transfers to intensive care), but with a potential economic expense (longer hospital stays and higher costs).

Rationale: Continuous positive airway pressure (CPAP) adherence is often poor in obstructive sleep apnea (OSA) and may be influenced by nasal resistance. CPAP with a reduction of expiratory pressure (CPAPflex) may reduce discomfort in those with high nasal resistance and improve adherence in this subgroup. Objectives: To evaluate the association of positive airway pressure (PAP) treatment adherence to nasal resistance and examine if CPAPflex improves adherence over CPAP in subjects with high nasal resistance. Methods: A randomized double-blind crossover trial of 4 weeks each of CPAPflex versus CPAP in subjects exposed to World Trade Center dust with OSA stratified by nasal resistance, measured by 4-Phase Rhinomanometry. Results: Three hundred seventeen subjects with OSA (mean, apnea–hypopnea index with 4% O(2) desaturation for hypopnea = 17 ± 14/h) were randomized. Overall, PAP adherence was poor, but adherence to CPAP (n = 239; mean hours per night [95% confidence interval (CI)]), 1.97 h (1.68 to 2.26) was greater than adherence to CPAPflex (n = 249; 1.65 h [1.39 to 1.91]; difference of 0.31 h [0.03; 0.6]; P

Background Healthcare workers (HCW) are presumed to be at increased risk of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection due to occupational exposure to infected patients. However, there has been little epidemiological research to assess these risks. Methods We conducted a prospective cohort study of HCW (n = 546) and non-healthcare workers (NHCW; n = 283) with no known prior SARS-CoV-2 infection who were recruited from a large U.S. university and two affiliated university hospitals. In this cross-sectional analysis of data collected at baseline, we examined SARS-CoV-2 infection status (as determined by presence of SARS-CoV-2 RNA in oropharyngeal swabs) by healthcare worker status and role. Results At baseline, 41 (5.0%) of the participants tested positive for SARS-CoV-2 infection, of whom 14 (34.2%) reported symptoms. The prevalence of SARS-CoV-2 infection was higher among HCW (7.3%) than in NHCW (0.4%), representing a 7.0% greater absolute risk (95% confidence interval for risk difference 4.7, 9.3%). The majority of infected HCW (62.5%) were nurses. Positive tests increased across the two weeks of cohort recruitment in line with rising confirmed cases in the hospitals and surrounding counties. Conclusions Overall, our results demonstrate that HCW had a higher prevalence of SARS-CoV-2 infection than NHCW. Continued follow-up of this cohort will enable us to monitor infection rates and examine risk factors for transmission.

Background The relationship between local hospital culture and transfusion rates following endovascular and surgical cardiovascular procedures has not been well studied. Methods and Results Patients undergoing coronary revascularization, aortic valve replacement, lower extremity peripheral vascular intervention, or carotid artery revascularization from up to 852 US hospitals in the Nationwide Readmissions Database were identified. Crude and risk‐standardized red blood cell transfusion rates were determined for each procedure. Pearson correlation coefficients were calculated between respective procedural transfusion rates. Median odds ratios were estimated to reflect between‐hospital variability in red blood cell transfusion rates following the same procedure for a given patient. There was wide variation in red blood cell transfusion rates across different procedures, from 2% following carotid endarterectomy to 29% following surgical aortic valve replacement. For surgical and endovascular modalities, transfusion rates at the same hospital were highly correlated for aortic valve replacement ( r =0.67; P r =0.56; P r =0.51; P r =0.19, P 2, highest for coronary artery bypass graft surgery and surgical aortic valve replacement, indicating substantial site variation in transfusion rates. Conclusions After adjustment for patient‐related factors, wide variation in red blood cell transfusion rates remained across surgical and endovascular procedures employed for the same cardiovascular condition. Transfusion rates following these procedures are highly correlated at individual hospitals and vary widely across hospitals. In aggregate, these findings suggest that local institutional culture significantly influences the decision to transfuse following invasive cardiovascular procedures and highlight the need for randomized data to inform such decisions.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a critical concern among healthcare workers (HCWs). Other studies have assessed SARS-CoV-2 virus and antibodies in HCWs, with disparate findings regarding risk based on role and demographics. Methods We screened 3904 employees and clinicians for SARS-CoV-2 virus positivity and serum immunoglobulin (Ig)G at a major New Jersey hospital from April 28 to June 30, 2020. We assessed positive tests in relation to demographic and occupational characteristics and prior coronavirus disease 2019 symptoms using multivariable logistic regression models. Results Thirteen participants (0.3%) tested positive for virus and 374 (9.6%) tested positive for IgG (total positive: 381 [9.8%]). Compared with participants with no patient care duties, the odds of positive testing (virus or antibodies) were higher for those with direct patient contact: below-median patient contact, adjusted odds ratio (aOR) = 1.71 and 95% confidence interval [CI] = 1.18–2.48; above-median patient contact, aOR = 1.98 and 95% CI = 1.35–2.91. The proportion of participants testing positive was highest for phlebotomists (23.9%), maintenance/housekeeping (17.3%), dining/food services (16.9%), and interpersonal/support roles (13.7%) despite lower levels of direct patient care duties. Positivity rates were lower among doctors (7.2%) and nurses (9.1%), roles with fewer underrepresented minorities. After adjusting for job role and patient care responsibilities and other factors, Black and Latinx workers had 2-fold increased odds of a positive test compared with white workers. Loss of smell, taste, and fever were associated with positive testing. Conclusions The HCW categories at highest risk for SARS-CoV-2 infection include support staff and underrepresented minorities with and without patient care responsibilities. Future work is needed to examine potential sources of community and nosocomial exposure among these understudied HCWs.

Background We report faculty affairs lessons from the formation and academic restructuring of Rutgers Biomedical and Health Sciences. Our approach may be a blueprint for development of a new track system that can be adapted by other institutions, after consideration of their own special circumstances. Methods We created new Appointments and Promotions guidelines consisting of one Tenure Track and four Non-Tenure Tracks, each with different missions. We restructured faculty performance evaluations to include mission-based criteria, an expanded rating scale, and specific expectations. After negotiating these new processes with our faculty union, we enacted central oversight to ensure uniform application of these processes and their associated criteria. We communicated the guidelines and the evaluation system widely. We created programs for universal mentoring, publishing education, diversity, and faculty development. Results All faculty in our seven schools went through track selection. Anxiety and incomplete understanding improved after implementation. Evaluations with expectations for the following year and an expanded scale for more nuanced assessment served as mentoring tools. Requirements for mentor assignments and diversity education created an atmosphere of nurturing and inclusion. Publications, extramural support, and faculty satisfaction increased after implementation of the guidelines. Conclusion Lessons included the need to review and learn from guidelines at other institutions, to create tracks that align with different jobs, the necessity for central oversight for uniform application of criteria, the need for extensive and frequent communication with faculty, and that fear of change is only reduced after evidence of success of a new structure. The most important lesson was that faculty rise to expectations when clear, ambitious criteria are delineated and universally applied.

ImportanceHealthcare workers are presumed to be at increased risk of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection due to occupational exposure to infected patients. However, no epidemiological study has examined the prevalence of SARS-CoV-2 infection in a cohort of healthcare workers during the early phase of community transmission.ObjectiveTo determine the baseline prevalence of SARS-CoV-2 infection in a cohort of previously undiagnosed healthcare workers and a comparison group of non-healthcare workers.DesignProspective cohort studySettingA large U.S. university and two affiliated university hospitalsParticipants546 health care workers and 283 non-health care workers with no known prior SARS-CoV-2 infectionExposureHealthcare worker status and roleMain outcome(s) and measure(s)SARS-CoV-2 infection status as determined by presence of SARS-CoV-2 RNA in oropharyngeal swabs.ResultsAt baseline, 41 (5.0%) of participants tested positive for SARS-CoV-2 infection, of whom 14 (34.2%) reported symptoms. The prevalence of SARS-CoV-2 infection was higher among healthcare workers (7.3%) than in non-healthcare workers (0.4%), representing a 7.0% greater absolute risk (95% confidence interval for risk difference 4.7%, 9.3%). The majority of infected healthcare workers (62.5%) worked as nurses. Positive tests increased across the two weeks of cohort recruitment in line with rising confirmed cases in the hospitals and surrounding counties.Conclusions and relevanceIn a prospective cohort conducted in the early phases of community transmission, healthcare workers had a higher prevalence of SARS-CoV-2 infection than non-healthcare workers, attesting to the occupational hazards of caring for patients in this crisis. Baseline data reported here will enable us to monitor the spread of infection and examine risk factors for transmission among healthcare workers. These results will inform optimal strategies for protecting the healthcare workforce, their families, and their patients.Clinicaltrials.gov registration number:NCT04336215Key pointsQuestionAmong previously undiagnosed individuals, is the prevalence of SARS-CoV-2 infection higher in U.S. healthcare workers compared to non-healthcare workers in the early phase of the U.S. COVID-19 epidemic?FindingsThe prevalence of SARS-CoV-2 infection was 7.3% in healthcare workers and 0.4% in non-healthcare workers, representing 7.0% greater absolute risk in the former (95% confidence interval for risk difference 4.7%, 9.3%). Infections were most common among nursing staff.MeaningHealth care workers, particularly those with high levels of close patient contact, may be particularly vulnerable to SARS-CoV-2 infection. Additional strategies are needed to protect these critical frontline workers.

As the coronavirus disease 2019 (COVID-19) pandemic sweeps across the world, the availability of viral transport medium (VTM) has become severely limited, contributing to delays in diagnosis and rationing of diagnostic testing. Given that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA has demonstrated stability, we posited that phosphate-buffered saline (PBS) may be a viable transport medium, as an alternative to VTM, for clinical real-time quantitative PCR (qPCR) testing. The intra-individual reliability and interindividual reliability of SARS-CoV-2 qPCR were assessed in clinical endotracheal secretion samples transported in VTM or PBS to evaluate the stability of the qPCR signal for three viral targets (N gene, ORF1ab, and S gene) when samples were stored in these media at room temperature for up to 18 hours. We report that the use of PBS as a transport medium allows high intra-individual and interindividual reliability, maintains viral stability, and compares with VTM in the detection of the three SARS-CoV-2 genes through 18 hours of storage. This study establishes PBS as a clinically useful medium that can be readily deployed for transporting and short-term preservation of specimens containing SARS-CoV-2. Use of PBS as a transport medium has the potential to increase testing capacity for SARS-CoV-2, aiding more widespread screening and early diagnosis of COVID-19.

OBJECTIVES: To present the consensus recommendations and supporting literature for RBC transfusions in general critically ill children from the Pediatric Critical Care Transfusion and Anemia Expertise Initiative.DESIGN: Consensus conference series of international, multidisciplinary experts in RBC transfusion management of critically ill children.METHODS: The panel of 38 experts developed evidence-based and, when evidence was lacking, expert-based recommendations and research priorities regarding RBC transfusions in critically ill children. The subgroup on RBC transfusion in general critically ill children included six experts. Electronic searches were conducted using PubMed, EMBASE, and Cochrane Library databases from 1980 to May 30, 2017, using a combination of keywords to define concepts of RBC transfusion and critically ill children. Recommendation consensus was obtained using the Research and Development/UCLA Appropriateness Method. The results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method.RESULTS: Three adjudicators reviewed 4,399 abstracts; 71 papers were read, and 17 were retained. Three papers were added manually. The general Transfusion and Anemia Expertise Initiative subgroup developed, and all Transfusion and Anemia Expertise Initiative members voted on two good practice statements, six recommendations, and 11 research questions; in all instances, agreement was reached (> 80%). The good practice statements suggest a framework for RBC transfusion in PICU patients. The good practice statements and recommendations focus on hemoglobin as a threshold and/or target. The research questions focus on hemoglobin and physiologic thresholds for RBC transfusion, alternatives, and risk/benefit ratio of transfusion.CONCLUSIONS: Transfusion and Anemia Expertise Initiative developed pediatric-specific good practice statements and recommendations regarding RBC transfusion management in the general PICU population, as well as recommendations to guide future research priorities. Clinical recommendations emphasized relevant hemoglobin thresholds, and research recommendations emphasized a need for further understanding of physiologic thresholds, alternatives to RBC transfusion, and hemoglobin thresholds in populations with limited pediatric literature.

BACKGROUND: Evidence from prospectively designed studies to guide on-site monitoring practices for randomized trials is limited. A cluster randomized study, nested within the Strategic Timing of AntiRetroviral Treatment (START) trial, was conducted to evaluate on-site monitoring. METHODS: Sites were randomized to either annual on-site monitoring or no on-site monitoring. All sites were centrally monitored, and local monitoring was carried out twice each year. Randomization was stratified by country and projected enrollment in START. The primary outcome was a participant level composite outcome including components for eligibility errors, consent violations, use of antiretroviral treatment not recommended by protocol, late reporting of START primary and secondary clinical endpoints (defined as the event being reported more than 6 months from occurrence), and data alteration and fraud. Logistic regression fixed effect hierarchical models were used to compare on-site versus no on-site monitoring for the primary composite outcome and its components. Odds ratios (ORs) and 95% confidence intervals (CIs) comparing on-site monitoring vs no on-site monitoring are cited. RESULTS: Ninety-nine sites (2,107 participants) were randomized to receive annual on-site monitoring and 97 sites (2,264 participants) were randomized to be monitored only centrally and locally. The two monitoring groups were well-balanced at entry. In the on-site monitoring group, 469 annual on-site monitoring visits were conducted, and 134 participants (6.4%) in 56 of 99 sites (57%) had a primary monitoring outcome. In the no on-site monitoring group, 85 participants (3.8%) in 34 of 97 sites (35%) had a primary monitoring outcome (OR=1.7; 95% CI: 1.1-2.7; p=0.03). Informed consent violations accounted for most outcomes in each group (56 versus 41 participants). The largest OR was for eligibility violations (OR=12.2; 95% CI: 1.8-85.2; p=0.01). The number of participants with a late START primary endpoint was similar for each monitoring group (23 versus 16 participants). Late START grade 4 and unscheduled hospitalization events were found for 34 participants in the on-site monitoring group and 19 participants in the no on-site monitoring group (OR=2.0; 95% CI: 1.1-3.7; p=0.02). There were no cases of data alteration or fraud. Based on the travel budget for on-site monitoring and the hours spent conducting on-site monitoring, the estimated cost of on-site monitoring was over $2 million. CONCLUSIONS: On-site monitoring led to the identification of more eligibility and consent violations and START clinical events being reported more than 6 months from occurrence as compared to no on-site monitoring. Considering the nature of the excess monitoring outcomes identified at sites receiving on-site monitoring, as well as the cost of on-site monitoring, the value to the START study was limited.

Monitoring the burden and spread of infection with the new coronavirus SARS-CoV-2, whether within small communities or in large geographical settings, is of paramount importance for public health purposes. Serology, which detects the host antibody response to the infection, is the most appropriate tool for this task, since virus-derived markers are most reliably detected during the acute phase of infection. Here we show that our ELISA protocol, which is based on antibody binding to the Receptor Binding Domain (RBD) of the S1 subunit of the viral Spike protein expressed as a novel fusion protein, detects antibody responses to SARS-CoV-2 infection and COVID-19 vaccination. We also show that our ELISA is accurate and versatile. It compares favorably with commercial assays widely used in clinical practice to determine exposure to SARS-CoV-2. Moreover, our protocol accommodates use of various blood- and non-blood-derived biospecimens, such as breast milk, as well as dried blood obtained with microsampling cartridges that are appropriate for remote collection. As a result, our RBD-based ELISA protocols are well suited for seroepidemiology and other large-scale studies requiring parsimonious sample collection outside of healthcare settings.

OBJECTIVE: To determine if adjusted mortality, walking ability or return home differed after hip fracture surgery between Canada and the USA. DESIGN: Secondary analysis of the Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair (FOCUS) trial data. SETTING: Data were collected from 47 American and Canadian hospitals. PARTICIPANTS: Overall, 2016 subjects with a hip fracture (USA = 1222 (60.6%); Canada = 794 (39.4%)) were randomized to a liberal or restrictive transfusion strategy. Subjects were 50 years and older, with cardiovascular disease and/or risk factors and hemoglobin

Advances in clinical research have led to reduced use of blood products. Judicious use has reduced the incidence of lung injury and circulatory overload. Testing of blood products for infectious agents has reduced their transmission.

OBJECTIVES: Hip fractures are associated with a high rate of morbidity and mortality, and successful ambulation after surgery is an important outcome in this patient population. This study aims to determine whether 25-hydroxyvitamin D (25(OH)D) or the Geriatric Nutritional Risk Index (GNRI) is associated with short term mortality or ability to walk after hip fracture surgery. METHODS: Patients undergoing hip fracture repair were included in this study. Mortality and walking ability were assessed at 30 and 60 days after hip fracture surgery. Pre-operative serum albumin and 25(OH)D were measured. Patients were characterized with 25(OH)D

Background Patients with cancer or other diagnoses associated with chronic anemia often receive red blood cell (RBC) transfusion as outpatients, but the effect of transfusion on functional status is not well demonstrated. Study design and methods To estimate the effect of transfusion on functional status and quality of life, we measured 6-minute walk test distance and fatigue- and dyspnea-related quality-of-life scores before and 1 week after RBC transfusion in 208 outpatients age ≥50 with at least one benign or malignant hematology/oncology diagnosis. To account for potential confounding effects of cancer treatment, patients were classified into two groups based on cancer treatment within 4 weeks of the study transfusion. Minimum clinically important improvements over baseline were 20 meters in walk test distance, 3 points in fatigue score, and 2 points in dyspnea score. Results The median improvement in unadjusted walk test distance was 20 meters overall and 30 meters in patients not receiving recent cancer treatment. Fatigue scores improved overall by a median of 3 points and by 4 points in patients without cancer treatment. There was no clinically important change in dyspnea scores. In multiple linear regression analysis, patients who maintained hemoglobin (Hb) levels of 8 g/dL or greater at 1 week posttransfusion, who had not received recent cancer treatment, and who did not require hospitalization during the study showed clinically important increases in mean walk test distance. Conclusions Red blood cell transfusion is associated with a modest, but clinically important improvement in walk test distance and fatigue score outcomes in adult hematology/oncology outpatients.

Blood transfusion is one of the most frequently used therapies worldwide and is associated with benefits, risks, and costs.To develop a set of evidence-based recommendations for patient blood management (PBM) and for research.The scientific committee developed 17 Population/Intervention/Comparison/Outcome (PICO) questions for red blood cell (RBC) transfusion in adult patients in 3 areas: preoperative anemia (3 questions), RBC transfusion thresholds (11 questions), and implementation of PBM programs (3 questions). These questions guided the literature search in 4 biomedical databases (MEDLINE, EMBASE, Cochrane Library, Transfusion Evidence Library), searched from inception to January 2018. Meta-analyses were conducted with the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology and the Evidence-to-Decision framework by 3 panels including clinical and scientific experts, nurses, patient representatives, and methodologists, to develop clinical recommendations during a consensus conference in Frankfurt/Main, Germany, in April 2018.From 17 607 literature citations associated with the 17 PICO questions, 145 studies, including 63 randomized clinical trials with 23 143 patients and 82 observational studies with more than 4 million patients, were analyzed. For preoperative anemia, 4 clinical and 3 research recommendations were developed, including the strong recommendation to detect and manage anemia sufficiently early before major elective surgery. For RBC transfusion thresholds, 4 clinical and 6 research recommendations were developed, including 2 strong clinical recommendations for critically ill but clinically stable intensive care patients with or without septic shock (recommended threshold for RBC transfusion, hemoglobin concentration7 g/dL) as well as for patients undergoing cardiac surgery (recommended threshold for RBC transfusion, hemoglobin concentration7.5 g/dL). For implementation of PBM programs, 2 clinical and 3 research recommendations were developed, including recommendations to implement comprehensive PBM programs and to use electronic decision support systems (both conditional recommendations) to improve appropriate RBC utilization.The 2018 PBM International Consensus Conference defined the current status of the PBM evidence base for practice and research purposes and established 10 clinical recommendations and 12 research recommendations for preoperative anemia, RBC transfusion thresholds for adults, and implementation of PBM programs. The relative paucity of strong evidence to answer many of the PICO questions supports the need for additional research and an international consensus for accepted definitions and hemoglobin thresholds, as well as clinically meaningful end points for multicenter trials.

Background:Randomized clinical trial findings support decreased red blood cell (RBC) transfusion and short-term tolerance of in-hospital anemia. However, long-term outcomes related to changes in transfusion practice have not been described. Objective:To describe the prevalence of anemia at and after hospital discharge and associated morbidity and mortality events. Design:Retrospective cohort study. Setting:Integrated health care delivery system with 21 hospitals serving 4 million members. Participants:445371 surviving adults who had 801261 hospitalizations between January 2010 and December 2014. Measurements:Hemoglobin levels and RBC transfusion, rehospitalization, and mortality events within 6 months of hospital discharge. Generalized estimating equations were used to examine trends over time, accounting for correlated observations and patient-level covariates. Results:From 2010 to 2014, the prevalence of moderate anemia (hemoglobin levels between 7 and 10 g/dL) at hospital discharge increased from 20% to 25% (P < 0.001) and RBC transfusion declined by 28% (39.8 to 28.5 RBC units per 1000 patients; P < 0.001). The proportion of patients whose moderate anemia had resolved within 6 months of hospital discharge decreased from 42% to 34% (P < 0.001), and RBC transfusion and rehospitalization within 6 months of hospital discharge decreased from 19% to 17% and 37% to 33%, respectively (P < 0.001 for both). During this period, the adjusted 6-month mortality rate decreased from 16.1% to 15.6% (P= 0.004) in patients with moderate anemia, in parallel with that of all others. Limitation:Possible unmeasured confounding. Conclusion:Anemia after hospitalization increased in parallel with decreased RBC transfusion. This increase was not accompanied by a rise in subsequent RBC use, rehospitalization, or mortality within 6 months of hospital discharge. Longitudinal analyses support the safety of practice recommendations to limit RBC transfusion and tolerate anemia during and after hospitalization. Primary Funding Source:National Heart, Lung, and Blood Institute.

More than 90% of allogeneic hematopoietic stem cell transplant (allo-HSCT) patients receive red blood cell (RBC) or platelet transfusions in the peritransplant period. We tested the hypothesis that transfusions are associated with development of severe acute graft-versus-host disease (grade III/IV aGvHD) or mortality in allo-HSCT in a retrospective study of 322 consecutive patients receiving allogeneic bone marrow or G-CSF-mobilized blood stem cell grafts for hematological malignancies. Counting RBC and platelet units between day −7 pre-transplant and +27 post-transplant, but excluding transfusions administered after a diagnosis of aGvHD, yielded medians of 5 RBC and 2 platelet units transfused. 63 patients (20%) developed a maximal grade of III–IV aGvHD with onset up to day 150 post-transplant (median aGvHD onset of 28 days). HLA mis-match (HR 2.4 (1.2, 4.7), p=0.01), and transfusion of > median number of RBC units (HR 2.1 (1.1, 3.7), p=0.02) were independently associated with greater risk of grade III–IV aGvHD in a multivariable analysis model. Disease risk strata (HR 1.7 (1.2, 2.4) for high risk vs. low risk, p=0.005) and transfusion of > median RBC units (HR 1.4 (1.0, 2.0), p=0.054) were independently associated with inferior overall survival. These data support our hypothesis that peritransplant RBC transfusions are associated with the risk of developing severe aGvHD and worse overall survival following allo-HSCT, and suggest that strategies to reduce routine RBC transfusion may favorably reduce GvHD incidence and severity.

LPS-induced TLR4 activation alters cellular bioenergetics and triggers proteolytic cleavage of AMPKα and HIF-1α expression in leukocytes. In human leukocytes, and more specifically neutrophils, AMPKα cleavage yields 55- and 35-kDa protein fragments. In this study, we address the mechanism by which AMPKα is cleaved and its relevance to human health. Our data indicate that AMPKα cleavage is linked to MMP9 expression and that both are required for mammalian target of rapamycin complex-1 and S6K1 activation and HIF-1α expression in LPS-stimulated human and mice leukocytes. Three key observations support this conclusion. First, no changes in AMPKα and TLR4 signaling intermediates (mammalian target of rapamycin complex-1/S6 kinase 1/HIF-1α) were detected in LPS-stimulated MMP9-deficient mice leukocytes. Second, rMMP9 cleaved human AMPKα ex vivo, producing degradation products similar in size to those detected following LPS stimulation. Third, MMP9 inhibitors prevented AMPKα degradation and HIF-1α expression in LPS-activated human leukocytes, whereas AMPK activators blocked MMP9 and HIF-1α expression. Significantly, AMPKα degradation, MMP9, and TLR4 signaling intermediates were all detected in leukocytes from patients with type 2 diabetes mellitus and patients following cardiopulmonary bypass surgery. Plasma from these two patient cohorts induced AMPKα cleavage and TLR4 signaling intermediates in healthy donor leukocytes and either a TLR4 inhibitor or polymyxin prevented these outcomes. Detection of AMPKα degradation, MMP9 expression, and TLR4 signaling intermediates described in this study in leukocytes, the most readily available human cells for clinical investigation, may provide a powerful tool for further exploring the role of TLR4 signaling in human diseases and lead to identification of new, context-specific therapeutic modalities for precision medicine.