Restrictive or Liberal Transfusion Strategy in Myocardial Infarction and Anemia.

BACKGROUND: A strategy of administering a transfusion only when the hemoglobin level falls below 7 or 8 g per deciliter has been widely adopted. However, patients with acute myocardial infarction may benefit from a higher hemoglobin level. METHODS: In this phase 3, interventional trial, we randomly assigned patients with myocardial infarction and a hemoglobin level of less than 10 g per deciliter to a restrictive transfusion strategy (hemoglobin cutoff for transfusion, 7 or 8 g per deciliter) or a liberal transfusion strategy (hemoglobin cutoff, <10 g per deciliter). The primary outcome was a composite of myocardial infarction or death at 30 days. RESULTS: A total of 3504 patients were included in the primary analysis. The mean (±SD) number of red-cell units that were transfused was 0.7±1.6 in the restrictive-strategy group and 2.5±2.3 in the liberal-strategy group. The mean hemoglobin level was 1.3 to 1.6 g per deciliter lower in the restrictive-strategy group than in the liberal-strategy group on days 1 to 3 after randomization. A primary-outcome event occurred in 295 of 1749 patients (16.9%) in the restrictive-strategy group and in 255 of 1755 patients (14.5%) in the liberal-strategy group (risk ratio modeled with multiple imputation for incomplete follow-up, 1.15; 95% confidence interval [CI], 0.99 to 1.34; P = 0.07). Death occurred in 9.9% of the patients with the restrictive strategy and in 8.3% of the patients with the liberal strategy (risk ratio, 1.19; 95% CI, 0.96 to 1.47); myocardial infarction occurred in 8.5% and 7.2% of the patients, respectively (risk ratio, 1.19; 95% CI, 0.94 to 1.49). CONCLUSIONS: In patients with acute myocardial infarction and anemia, a liberal transfusion strategy did not significantly reduce the risk of recurrent myocardial infarction or death at 30 days. However, potential harms of a restrictive transfusion strategy cannot be excluded. (Funded by the National Heart, Lung, and Blood Institute and others; MINT ClinicalTrials.gov number, NCT02981407.).

How I treat anemia with red blood cell transfusion and iron.

Severe anemia is commonly treated with red blood cell transfusion. Clinical trials have demonstrated that a restrictive transfusion strategy of 7 to 8 g/dL is as safe as a liberal transfusion strategy of 9 to 10 g/dL in many clinical settings. Evidence is lacking for subgroups of patients, including those with preexisting coronary artery disease, acute myocardial infarction, congestive heart failure, and myelodysplastic neoplasms. We present 3 clinical vignettes that highlight the clinical challenges in caring for patients with coronary artery disease with gastrointestinal bleeding, congestive heart failure, or myelodysplastic neoplasms. We emphasize that transfusion practice should be guided by patient symptoms and preferences in conjunction with the patient's 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.

Spinal Anesthesia or General Anesthesia for Hip Surgery in Older Adults.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.).

Long-term Outcomes with Spinal versus General Anesthesia for Hip Fracture Surgery: A Randomized Trial.

BACKGROUND: The effects of spinal versus general anesthesia on long-term outcomes have not been well studied. This study tested the hypothesis that spinal anesthesia is associated with better long-term survival and functional recovery than general anesthesia. METHODS: A prespecified analysis was conducted of long-term outcomes of a completed randomized superiority trial that compared spinal anesthesia versus general anesthesia for hip fracture repair. Participants included previously ambulatory patients 50 yr of age or older at 46 U.S. and Canadian hospitals. Patients were randomized 1:1 to spinal or general anesthesia, stratified by sex, fracture type, and study site. Outcome assessors and investigators involved in the data analysis were masked to the treatment arm. Outcomes included survival at up to 365 days after randomization (primary); recovery of ambulation among 365-day survivors; and composite endpoints for death or new inability to ambulate and death or new nursing home residence at 365 days. Patients were included in the analysis as randomized. RESULTS: A total of 1,600 patients were enrolled between February 12, 2016, and February 18, 2021; 795 were assigned to spinal anesthesia, and 805 were assigned to general anesthesia. Among 1,599 patients who underwent surgery, vital status information at or beyond the final study interview (conducted at approximately 365 days after randomization) was available for 1,427 (89.2%). Survival did not differ by treatment arm; at 365 days after randomization, there were 98 deaths in patients assigned to spinal anesthesia versus 92 deaths in patients assigned to general anesthesia (hazard ratio, 1.08; 95% CI, 0.81 to 1.44, P = 0.59). Recovery of ambulation among patients who survived a year did not differ by type of anesthesia (adjusted odds ratio for spinal vs. general, 0.87; 95% CI, 0.67 to 1.14; P = 0.31). Other outcomes did not differ by treatment arm. CONCLUSIONS: Long-term outcomes were similar with spinal versus general anesthesia.

Rationale and design for the myocardial ischemia and transfusion (MINT) randomized clinical trial.

BACKGROUND: 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. METHODS: 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 hemoglobin <10 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 end point is a composite of all-cause death or recurrent MI through 30 days following randomization. Secondary end points 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 end points. CONCLUSIONS: The MINT trial will inform RBC transfusion practice in patients with acute MI.

An analysis of quality of life and functional outcomes as reported in randomized trials for red cell transfusions.

BACKGROUND: Meta-analyses of randomized controlled trials (RCTs) evaluating thresholds for red blood cell (RBC) transfusion typically focus on mortality; however, other outcomes are highly relevant. The aim of this study is to summarize the effects of different transfusion thresholds on the outcomes of quality of life (QoL) and function. STUDY DESIGN: We extracted data from RCTs identified in a recently published Cochrane systematic review. Primary analysis was descriptive. RESULTS: A total of 23 RCTs with 13,743 adult participants were included. Fifteen RCTs included patients in the postoperative period, of which 9 RCTs were conducted in hip (n = 3024) and 6 (n = 8672) in cardiac surgeries; 5 RCTs (n = 489) were in patients with hematological malignancies; 2 in the setting of bleeding (gastrointestinal bleed [n = 936] and postpartum [n = 521]); and one RCT (n = 936) included critically ill patients. QoL and function were reported using a variety of questionnaires and tools. The timing of assessments varied between trials. No clear clinical differences in QoL outcomes were identified in comparisons between restrictive and liberal transfusion thresholds. DISCUSSION: There is no evidence that a liberal transfusion strategy improves QoL and functional outcomes. However, the substantial limitations of many included studies indicate the need for further well-designed and adequately powered trials.

Risks for Anaphylaxis With Intravenous Iron Formulations : A Retrospective Cohort Study.

BACKGROUND: The risks for anaphylaxis among intravenous (IV) iron products currently in use have not been assessed. OBJECTIVE: To compare risks for anaphylaxis among 5 IV iron products that are used frequently. DESIGN: Retrospective cohort study using a target trial emulation framework. SETTING: Medicare fee-for-service data with Part D coverage between July 2013 and December 2018. PARTICIPANTS: Older adults receiving their first administration of IV iron. MEASUREMENTS: 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. RESULTS: 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. LIMITATION: Generalizability to non-Medicare populations. CONCLUSION: 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. PRIMARY FUNDING SOURCE: None.

Pain, Analgesic Use, and Patient Satisfaction With Spinal Versus General Anesthesia for Hip Fracture Surgery : A Randomized Clinical Trial.

BACKGROUND: 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. OBJECTIVE: To compare pain, analgesic use, and satisfaction after hip fracture surgery with spinal versus general anesthesia. DESIGN: Preplanned secondary analysis of a pragmatic randomized trial. (ClinicalTrials.gov: NCT02507505). SETTING: 46 U.S. and Canadian hospitals. PARTICIPANTS: Patients aged 50 years or older undergoing hip fracture surgery. INTERVENTION: Spinal or general anesthesia. MEASUREMENTS: Pain on postoperative days 1 through 3; 60-, 180-, and 365-day pain and prescription analgesic use; and satisfaction with care. RESULTS: 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. LIMITATION: Missing outcome data and multiple outcomes assessed. CONCLUSION: 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. PRIMARY FUNDING SOURCE: Patient-Centered Outcomes Research Institute.

Red Blood Cell Transfusion: 2023 AABB International Guidelines.

Importance: Red blood cell transfusion is a common medical intervention with benefits and harms. Objective: To provide recommendations for use of red blood cell transfusion in adults and children. Evidence Review: Standards for trustworthy guidelines were followed, including using Grading of Recommendations Assessment, Development and Evaluation methods, managing conflicts of interest, and making values and preferences explicit. Evidence from systematic reviews of randomized controlled trials was reviewed. Findings: For adults, 45 randomized controlled trials with 20 599 participants compared restrictive hemoglobin-based transfusion thresholds, typically 7 to 8 g/dL, with liberal transfusion thresholds of 9 to 10 g/dL. For pediatric patients, 7 randomized controlled trials with 2730 participants compared a variety of restrictive and liberal transfusion thresholds. For most patient populations, results provided moderate quality evidence that restrictive transfusion thresholds did not adversely affect patient-important outcomes. Recommendation 1: for hospitalized adult patients who are hemodynamically stable, the international panel recommends a restrictive transfusion strategy considering transfusion when the hemoglobin concentration is less than 7 g/dL (strong recommendation, moderate certainty evidence). In accordance with the restrictive strategy threshold used in most trials, clinicians may choose a threshold of 7.5 g/dL for patients undergoing cardiac surgery and 8 g/dL for those undergoing orthopedic surgery or those with preexisting cardiovascular disease. Recommendation 2: for hospitalized adult patients with hematologic and oncologic disorders, the panel suggests a restrictive transfusion strategy considering transfusion when the hemoglobin concentration is less than 7 g/dL (conditional recommendations, low certainty evidence). Recommendation 3: for critically ill children and those at risk of critical illness who are hemodynamically stable and without a hemoglobinopathy, cyanotic cardiac condition, or severe hypoxemia, the international panel recommends a restrictive transfusion strategy considering transfusion when the hemoglobin concentration is less than 7 g/dL (strong recommendation, moderate certainty evidence). Recommendation 4: for hemodynamically stable children with congenital heart disease, the international panel suggests a transfusion threshold that is based on the cardiac abnormality and stage of surgical repair: 7 g/dL (biventricular repair), 9 g/dL (single-ventricle palliation), or 7 to 9 g/dL (uncorrected congenital heart disease) (conditional recommendation, low certainty evidence). Conclusions and Relevance: It is good practice to consider overall clinical context and alternative therapies to transfusion when making transfusion decisions about an individual patient.

Outcomes with spinal versus general anesthesia for patients with and without preoperative cognitive impairment: Secondary analysis of a randomized clinical trial.

INTRODUCTION: The effect of spinal versus general anesthesia on the risk of postoperative delirium or other outcomes for patients with or without cognitive impairment (including dementia) is unknown. METHODS: Post hoc secondary analysis of a multicenter pragmatic trial comparing spinal versus general anesthesia for adults aged 50 years or older undergoing hip fracture surgery. RESULTS: Among patients randomized to spinal versus general anesthesia, new or worsened delirium occurred in 100/295 (33.9%) versus 107/283 (37.8%; odds ratio [OR] 0.85; 95% confidence interval [CI] 0.60 to 1.19) among persons with cognitive impairment and 70/432 (16.2%) versus 71/445 (16.0%) among persons without cognitive impairment (OR 1.02; 95% CI 0.71 to 1.47, p = 0.46 for interaction). Delirium severity, in-hospital complications, and 60-day functional recovery did not differ by anesthesia type in patients with or without cognitive impairment. DISCUSSION: Anesthesia type is not associated with differences in delirium and functional outcomes among persons with or without cognitive impairment.

Determinants and Dynamics of SARS-CoV-2 Infection in a Diverse Population: 6-Month Evaluation of a Prospective Cohort Study.

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.

Plasma trial: Pilot randomized clinical trial to determine safety and efficacy of plasma transfusions.

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 <40,000/µl, or congenital or acquired coagulation disorders unresponsive to plasma. We randomly allocated patients stratified by hospital and history of cirrhosis to receive plasma transfusion (10-15 cc/kg) or no transfusion. The primary outcome was change in hemoglobin concentration within 2 days of procedure. RESULTS: We enrolled 57 patients, mean age 56.0, 34 (59.6%) with cirrhosis, and mean INR 1.92 (SD = 0.27). In the intention to treat analysis, there were 10 of 27 (38.5%) participants in the plasma arm with a post procedure INR <1.5 and one of 30 (3.6%) in the no treatment arm (p < .01). The mean INR after receiving plasma transfusion was -0.24 (SD 0.26) lower than baseline. The change from pre-procedure hemoglobin level to lowest level within 2 days was -0.6 (SD = 1.0) in the plasma transfusion arm and -0.4 (SD = 0.6) in the no transfusion arm (p = .29). Adverse outcomes were uncommon. DISCUSSION: We found no differences in change in hemoglobin concentration in those treated with plasma compared to no treatment. The change in INR was small and corrected to less than 1.5 in minority of patients. Large trials are required to establish if plasma is safe and efficacious.

Transfusion thresholds for guiding red blood cell transfusion.

BACKGROUND: The optimal haemoglobin threshold for use of red blood cell (RBC) transfusions in anaemic patients remains an active field of research. Blood is a scarce resource, and in some countries, transfusions are less safe than in others because of inadequate testing for viral pathogens. If a liberal transfusion policy does not improve clinical outcomes, or if it is equivalent, then adopting a more restrictive approach could be recognised as the standard of care.  OBJECTIVES: The aim of this review update was to compare 30-day mortality and other clinical outcomes for participants randomised to restrictive versus liberal red blood cell (RBC) transfusion thresholds (triggers) for all clinical conditions. The restrictive transfusion threshold uses a lower haemoglobin concentration as a threshold for transfusion (most commonly, 7.0 g/dL to 8.0 g/dL), and the liberal transfusion threshold uses a higher haemoglobin concentration as a threshold for transfusion (most commonly, 9.0 g/dL to 10.0 g/dL). SEARCH METHODS: We identified trials through updated searches: CENTRAL (2020, Issue 11), MEDLINE (1946 to November 2020), Embase (1974 to November 2020), Transfusion Evidence Library (1950 to November 2020), Web of Science Conference Proceedings Citation Index (1990 to November 2020), and trial registries (November 2020). We  checked the reference lists of other published reviews and relevant papers to identify additional trials. We were aware of one trial identified in earlier searching that was in the process of being published (in February 2021), and we were able to include it before this review was finalised. SELECTION CRITERIA: We included randomised trials of surgical or medical participants that recruited adults or children, or both. We excluded studies that focused on neonates. Eligible trials assigned intervention groups on the basis of different transfusion schedules or thresholds or 'triggers'. These thresholds would be defined by a haemoglobin (Hb) or haematocrit (Hct) concentration below which an RBC transfusion would be administered; the haemoglobin concentration remains the most commonly applied marker of the need for RBC transfusion in clinical practice. We included trials in which investigators had allocated participants to higher thresholds or more liberal transfusion strategies compared to more restrictive ones, which might include no transfusion. As in previous versions of this review, we did not exclude unregistered trials published after 2010 (as per the policy of the Cochrane Injuries Group, 2015), however, we did conduct analyses to consider the differential impact of results of trials for which prospective registration could not be confirmed.   DATA COLLECTION AND ANALYSIS: We identified trials for inclusion and extracted data using Cochrane methods. We pooled risk ratios of clinical outcomes across trials using a random-effects model. Two review authors independently extracted data and assessed risk of bias. We conducted predefined analyses by clinical subgroups. We defined participants randomly allocated to the lower transfusion threshold as being in the 'restrictive transfusion' group and those randomly allocated to the higher transfusion threshold as being in the 'liberal transfusion' group. MAIN RESULTS: A total of 48 trials, involving data from 21,433 participants (at baseline), across a range of clinical contexts (e.g. orthopaedic, cardiac, or vascular surgery; critical care; acute blood loss (including gastrointestinal bleeding); acute coronary syndrome; cancer; leukaemia; haematological malignancies), met the eligibility criteria. The haemoglobin concentration used to define the restrictive transfusion group in most trials (36) was between 7.0 g/dL and 8.0 g/dL.  Most trials included only adults; three trials focused on children. The included studies were generally at low risk of bias for key domains including allocation concealment and incomplete outcome data. Restrictive transfusion strategies reduced the risk of receiving at least one RBC transfusion by 41% across a broad range of clinical contexts (risk ratio (RR) 0.59, 95% confidence interval (CI) 0.53 to 0.66; 42 studies, 20,057 participants; high-quality evidence), with a large amount of heterogeneity between trials (I² = 96%). Overall, restrictive transfusion strategies did not increase or decrease the risk of 30-day mortality compared with liberal transfusion strategies (RR 0.99, 95% CI 0.86 to 1.15; 31 studies, 16,729 participants; I² = 30%; moderate-quality evidence) or any of the other outcomes assessed (i.e. cardiac events (low-quality evidence), myocardial infarction, stroke, thromboembolism (all high-quality evidence)). High-quality evidence shows that the liberal transfusion threshold did not affect the risk of infection (pneumonia, wound infection, or bacteraemia). Transfusion-specific reactions are uncommon and were inconsistently reported within trials. We noted less certainty in the strength of evidence to support the safety of restrictive transfusion thresholds for the following predefined clinical subgroups: myocardial infarction, vascular surgery, haematological malignancies, and chronic bone-marrow disorders. AUTHORS' CONCLUSIONS: Transfusion at a restrictive haemoglobin concentration decreased the proportion of people exposed to RBC transfusion by 41% across a broad range of clinical contexts. Across all trials, no evidence suggests that a restrictive transfusion strategy impacted 30-day mortality, mortality at other time points, or morbidity (i.e. cardiac events, myocardial infarction, stroke, pneumonia, thromboembolism, infection) compared with a liberal transfusion strategy. Despite including 17 more randomised trials (and 8846 participants), data remain insufficient to inform the safety of transfusion policies in important and selected clinical contexts, such as myocardial infarction, chronic cardiovascular disease, neurological injury or traumatic brain injury, stroke, thrombocytopenia, and cancer or haematological malignancies, including chronic bone marrow failure.  Further work is needed to improve our understanding of outcomes other than mortality. Most trials compared only two separate thresholds for haemoglobin concentration, which may not identify the actual optimal threshold for transfusion in a particular patient. Haemoglobin concentration may not be the most informative marker of the need for transfusion in individual patients with different degrees of physiological adaptation to anaemia. Notwithstanding these issues, overall findings provide good evidence that transfusions with allogeneic RBCs can be avoided in most patients with haemoglobin thresholds between the range of 7.0 g/dL and 8.0 g/dL. Some patient subgroups might benefit from RBCs to maintain higher haemoglobin concentrations; research efforts should focus on these clinical contexts.

Prevalence of SARS-CoV-2 infection in previously undiagnosed health care workers in New Jersey, at the onset of the U.S. COVID-19 pandemic.

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.

Long-Term Outcomes Among Patients Discharged From the Hospital With Moderate Anemia: A Retrospective Cohort Study.

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: 445 371 surviving adults who had 801 261 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.

Blood utilization in five Chinese hospitals shows low hemoglobin thresholds in medical patients.

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.