Association between sarcopenia and postoperative complications in patients undergoing surgery for gastrointestinal or hepato-pancreatico-biliary cancer.

BACKGROUND AND OBJECTIVES: Despite surgical advances, postoperative complications persist, affecting oncologic outcomes and increasing treatment costs. It is important to identify a marker that can predict postoperative complications, which can help prehabilitate patients before surgery. This study evaluated sarcopenia as a predictive marker of postoperative complications in patients undergoing surgery for gastrointestinal (GI) or hepato-pancreatico-biliary (HPB) cancer. METHODS: Sarcopenia was assessed using the skeletal muscle index at the third lumbar vertebra on abdominal computed tomography. The predictive ability of sarcopenia was evaluated by adjusting for other clinicopathological factors. RESULTS: Of the 210 patients, 81 (38.57%) were sarcopenic. The overall morbidity and mortality were 33.81% and 2.86%, respectively. Major complications (Clavien-Dindo Grade ≥ III) were observed in 10.95% patients and sarcopenic patients were significantly more likely to develop major complications (p = 1.42 × 10-10 ). Sarcopenia (p = 6.13 × 10-6 ; odds ratio = 12.29) independently predicted postoperative complications and prolonged hospital stay (p = 0.01). CONCLUSION: Sarcopenia objectively predicted the development of postoperative complications and prolonged hospital stay in patients undergoing surgery for GI or HPB cancer. This may facilitate the prehabilitation of patients planned for surgery to reduce the risk of complications.

Traumatic respiratory failure and veno-venous extracorporeal membrane oxygenation support.

BACKGROUND: Respiratory failure (RF) is a common cause of death and morbid complication in trauma patients. Extracorporeal membrane oxygenation (ECMO) is increasingly used in adults with RF refractory to invasive mechanical ventilation. However, use of ECMO remains limited for this patient population as they often have contraindications for anticoagulation. STUDY DESIGN: Medical records were retroactively searched for all adult patients who were admitted to the trauma service and received veno-venous ECMO (VV ECMO) support between June 2015 and August 2018. Survival to discharge and ECMO-related complications were collected and analyzed. RESULTS: Fifteen patients from a large Level I trauma center met the criteria. The median PaO2/FiO2 ratio was 53.0 (IQR, 27.0-76.0), median injury severity score was 34.0 (IQR, 27.0-43.0), and the median duration of ECMO support was 11 days (IQR, 7.5-20.0). For this cohort, the survival-to-discharge rate was 87% (13/15). The incidence of neurologic complications was 13%, and deep vein thrombosis was reported in two cases (13%). CONCLUSIONS: Survival rates of trauma patients in this study are equivalent to, or may exceed, those of non-trauma patients who receive ECMO support for other types of RF. With the employment of a multidisciplinary team assessment and proper patient selection, early cannulation, traumatic RF may be safely supported with VV ECMO in experienced centers.

Effect of Ascorbic Acid, Corticosteroids, and Thiamine on Organ Injury in Septic Shock: The ACTS Randomized Clinical Trial.

IMPORTANCE: The combination of ascorbic acid, corticosteroids, and thiamine has been identified as a potential therapy for septic shock. OBJECTIVE: To determine whether the combination of ascorbic acid, corticosteroids, and thiamine attenuates organ injury in patients with septic shock. DESIGN, SETTING, AND PARTICIPANTS: Randomized, blinded, multicenter clinical trial of ascorbic acid, corticosteroids, and thiamine vs placebo for adult patients with septic shock. Two hundred five patients were enrolled between February 9, 2018, and October 27, 2019, at 14 centers in the United States. Follow-up continued until November 26, 2019. INTERVENTIONS: Patients were randomly assigned to receive parenteral ascorbic acid (1500 mg), hydrocortisone (50 mg), and thiamine (100 mg) every 6 hours for 4 days (n = 103) or placebo in matching volumes at the same time points (n = 102). MAIN OUTCOMES AND MEASURES: The primary outcome was change in the Sequential Organ Failure Assessment (SOFA) score (range, 0-24; 0 = best) between enrollment and 72 hours. Key secondary outcomes included kidney failure and 30-day mortality. Patients who received at least 1 dose of study drug were included in analyses. RESULTS: Among 205 randomized patients (mean age, 68 [SD, 15] years; 90 [44%] women), 200 (98%) received at least 1 dose of study drug, completed the trial, and were included in the analyses (101 with intervention and 99 with placebo group). Overall, there was no statistically significant interaction between time and treatment group with regard to SOFA score over the 72 hours after enrollment (mean SOFA score change from 9.1 to 4.4 [-4.7] points with intervention vs 9.2 to 5.1 [-4.1] points with placebo; adjusted mean difference, -0.8; 95% CI, -1.7 to 0.2; P = .12 for interaction). There was no statistically significant difference in the incidence of kidney failure (31.7% with intervention vs 27.3% with placebo; adjusted risk difference, 0.03; 95% CI, -0.1 to 0.2; P = .58) or in 30-day mortality (34.7% vs 29.3%, respectively; hazard ratio, 1.3; 95% CI, 0.8-2.2; P = .26). The most common serious adverse events were hyperglycemia (12 patients with intervention and 7 patients with placebo), hypernatremia (11 and 7 patients, respectively), and new hospital-acquired infection (13 and 12 patients, respectively). CONCLUSIONS AND RELEVANCE: In patients with septic shock, the combination of ascorbic acid, corticosteroids, and thiamine, compared with placebo, did not result in a statistically significant reduction in SOFA score during the first 72 hours after enrollment. These data do not support routine use of this combination therapy for patients with septic shock. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03389555.

HVNI vs NIPPV in the treatment of acute decompensated heart failure: Subgroup analysis of a multi-center trial in the ED.

BACKGROUND AND OBJECTIVE: Managing respiratory failure (RF) secondary to acute decompensated heart failure (ADHF) with non-invasive positive-pressure ventilation (NIPPV) has been shown to significantly improve morbidity and mortality in patients presenting to the emergency department (ED). This subgroup analysis compares high-velocity nasal insufflation (HVNI), a form of high-flow nasal cannula, with NIPPV in the treatment of RF secondary to ADHF with respect to therapy failure, as indicated by the requirement for intubation or all-cause arm failure including subjective crossover to the alternate therapy. METHODS: The subgroup analysis is from a larger randomized control trial of adults presenting to the ED with RF requiring NIPPV support. Patients were randomly selected to therapy, and subgroup selection was established a priori in the original study as a discharge diagnosis. The primary outcome was therapy failure at 72 h after enrolment. RESULTS: Subgroup analysis included a total of 22 HVNI and 20 NIPPV patients which fit discharge diagnosis ADHF. Baseline patient characteristics were not statistically significant. Primary outcomes were not statistically significant: intubation rate (p = 1.000), therapy success (p = 1.000). Repeated measures (vitals, dyspnea, blood gases) showed comparable differences over initial 4 h. Physicians scored HVNI superior on patient comfort/tolerance (p < 0.001), ease of use (p = 0.004), and monitoring (p = 0.036). Limitations were technical inability to blind the clinician team and lack of power of the subgroup analysis. CONCLUSION: In conclusion, this subgroup analysis suggests HVNI may be non-inferior to NIPPV in patients with respiratory failure secondary to ADHF that do not need emergent intubation.

Correction to: Do Insurance Mandates Affect Racial Disparities in Outcomes for Children with Autism?

The original version of this article unfortunately contained a mistake in the analysis of the Tables 4 and 5.

High-Velocity Nasal Insufflation in the Treatment of Respiratory Failure: A Randomized Clinical Trial.

STUDY OBJECTIVE: We compare high-velocity nasal insufflation, a form of high-flow nasal cannula, with noninvasive positive-pressure ventilation in the treatment of undifferentiated respiratory failure with respect to therapy failure, as indicated by requirement for endotracheal intubation or cross over to the alternative therapy. METHODS: This was a multicenter, randomized trial of adults presenting to the emergency department (ED) with respiratory failure requiring noninvasive positive-pressure ventilation. Patients were randomly assigned to high-velocity nasal insufflation (initial flow 35 L/min; temperature 35°C (95°F) to 37°C (98.6°F); FiO2 1.0) or noninvasive positive-pressure ventilation using an oronasal mask (inspiratory positive airway pressure 10 cm H2O; expiratory positive airway pressure 5 cm H2O). The primary outcome was therapy failure at 72 hours after enrollment. A subjective outcome of crossover was allowed as a risk mitigation to support deferment of informed consent. Noninferiority margins were set at 15 and 20 percentage points, respectively. RESULTS: A total of 204 patients were enrolled and included in the analysis, randomized to high-velocity nasal insufflation (104) and noninvasive positive-pressure ventilation (100). The intubation rate (high-velocity nasal insufflation=7%; noninvasive positive-pressure ventilation=13%; risk difference=-6%; 95% confidence interval -14% to 2%) and any failure of the assigned arm (high-velocity nasal insufflation=26%; noninvasive positive-pressure ventilation=17%; risk difference 9%; confidence interval -2% to 20%) at 72 hours met noninferiority. The effect on PCO2 over time was similar in the entire study population and in patients with baseline hypercapnia. Vital signs and blood gas analyses improved similarly over time. The primary limitation was the technical inability to blind the clinical team. CONCLUSION: High-velocity nasal insufflation is noninferior to noninvasive positive-pressure ventilation for the treatment of undifferentiated respiratory failure in adult patients presenting to the ED.

Ascorbic acid, corticosteroids, and thiamine in sepsis: a review of the biologic rationale and the present state of clinical evaluation.

The combination of thiamine, ascorbic acid, and hydrocortisone has recently emerged as a potential adjunctive therapy to antibiotics, infectious source control, and supportive care for patients with sepsis and septic shock. In the present manuscript, we provide a comprehensive review of the pathophysiologic basis and supporting research for each element of the thiamine, ascorbic acid, and hydrocortisone drug combination in sepsis. In addition, we describe potential areas of synergy between these therapies and discuss the strengths/weaknesses of the two studies to date which have evaluated the drug combination in patients with severe infection. Finally, we describe the current state of current clinical practice as it relates to the thiamine, ascorbic acid, and hydrocortisone combination and present an overview of the randomized, placebo-controlled, multi-center Ascorbic acid, Corticosteroids, and Thiamine in Sepsis (ACTS) trial and other planned/ongoing randomized clinical trials.

An investigation of factors predicting the type of bladder antimuscarinics initiated in Medicare nursing homes residents.

BACKGROUND: To examine factors predicting type of bladder antimuscarinics (BAM) initiated in nursing home (NH) residents. METHODS: Incident BAM initiators following NH admission were identified by constructing a retrospective cohort from Medicare files and Minimum Data Set (MDS). Participants included all residents 65 years and older admitted in Medicare-certified NH between January 1, 2007 and December 31, 2008 who were prescribed BAM and had continuous Medicare (Part A, B, and D) enrollment. Patient characteristics, medications, and comorbidities were derived from Medicare enrollment and claims. NH characteristics and health status were derived from MDS assessments. The outcome was defined as type of BAM initiated after admission (selective, non-selective extended release, non-selective immediate release). Multinomial logistic regression using generalized estimating equation methodology determined which factors predicted the type of BAM initiated. RESULTS: Twelve thousand eight hundred ninety-nine NH residents initiating BAM therapy were identified; 13.38% of new users were prescribed selective BAM, 45.56% non-selective extended release, and 41.07% non-selective immediate release medications. In both sexes, significant predictors of BAM included region of nursing home, body mass index, cognitive performance score, frailty measures, activities of daily living, and measures of bladder continence. In women, history of fracture and fall-related injuries were significant predictors of type of BAM use, while race and indicators of balance were significant predictors of type of BAM use in men. Non-pharmacological continence management strategies were not predictive of type of BAM initiation. CONCLUSIONS: Several factors are important in predicting type of BAM initiation in both women and men, but other factors are sex-specific. Some observed factors predicting the type of BAM initiated, such as other medications use, body mass index, or provider-related factors are potentially modifiable and could be used in targeted interventions to help optimize BAM use in this population. TRIAL REGISTRATION: Not applicable.

Do Insurance Mandates Affect Racial Disparities in Outcomes for Children with Autism?

Objective The study investigated whether state mandates for private insurers to provide services for children with autism influence racial disparities in outcomes. Methods The study used 2005/2006 and 2009/2010 waves of the National Survey of Children with Special Health Care Needs. Children with a current diagnosis of autism were included in the sample. Children residing in 14 states and the District of Columbia that were not covered by the mandate in the 2005/2006 survey, but were covered in the 2009/2010 survey, served as the mandate group. Children residing in 32 states that were not covered by a mandate in either wave served as the comparison group. Outcome measures assessed included care quality, family economics, and child health. A difference-in-difference-in-differences (DDD) approach was used to assess the impact of the mandates on racial disparities in outcomes. Results Non-white children had less access to family-centered care compared to white children in both waves of data, but this difference was not apparent across mandate and comparison states as only the comparison states had significant differences. Parents of non-white children reported paying less in annual out-of-pocket expenses compared to parents of white children across waves and groups. DDD estimates did not provide evidence that the mandates had statistically significant effects on improving or worsening racial disparities for any outcome measure. Conclusions This study did not find evidence that state mandates on private insurers affected racial disparities in outcomes for children with autism.

Plasma cytokines IL-6, IL-8, and IL-10 are associated with the development of acute respiratory distress syndrome in patients with severe traumatic brain injury.

BACKGROUND: Patients with severe traumatic brain injury (TBI) are at risk of the development of acute respiratory distress syndrome (ARDS). TBI and ARDS pathophysiologic mechanisms are known to independently involve significant inflammatory responses. The literature on the association between plasma inflammatory cytokines and ARDS in patients with TBI is sparse. METHODS: The study was a secondary analysis of the safety of a randomized trial of erythropoietin and transfusion threshold in patients with severe TBI. Inflammatory markers within the first 24 hours after injury were compared in patients who developed ARDS and patients without ARDS, using Cox proportional hazards models. RESULTS: There were 200 patients enrolled in the study. The majority of plasma and cerebrospinal fluid (CSF) cytokine levels were obtained within 6 hours. Plasma proinflammatory markers IL-6 and IL-8 and anti-inflammatory marker IL-10 were associated with the development of ARDS (adjusted hazard ratio (HR) = 1.55, confidence interval (CI) = 1.14, 2.11, P = 0.005 for IL-6; adjusted HR = 1.32, CI = 1.10, 1.59, P = 0.003 for IL-8). CONCLUSION: Plasma markers of IL-6, IL-8, and IL-10 are associated with ARDS in patients with severe TBI. TRIAL REGISTRATION: NCT00313716 registered 4/2006.

Using voluntary reports from physicians to learn from diagnostic errors in emergency medicine.

OBJECTIVES: Diagnostic errors are common in the emergency department (ED), but few studies have comprehensively evaluated their types and origins. We analysed incidents reported by ED physicians to determine disease conditions, contributory factors and patient harm associated with ED-related diagnostic errors. METHODS: Between 1 March 2009 and 31 December 2013, ED physicians reported 509 incidents using a department-specific voluntary incident-reporting system that we implemented at two large academic hospital-affiliated EDs. For this study, we analysed 209 incidents related to diagnosis. A quality assurance team led by an ED physician champion reviewed each incident and interviewed physicians when necessary to confirm the presence/absence of diagnostic error and to determine the contributory factors. We generated descriptive statistics quantifying disease conditions involved, contributory factors and patient harm from errors. RESULTS: Among the 209 incidents, we identified 214 diagnostic errors associated with 65 unique diseases/conditions, including sepsis (9.6%), acute coronary syndrome (9.1%), fractures (8.6%) and vascular injuries (8.6%). Contributory factors included cognitive (n=317), system related (n=192) and non-remedial (n=106). Cognitive factors included faulty information verification (41.3%) and faulty information processing (30.6%) whereas system factors included high workload (34.4%) and inefficient ED processes (40.1%). Non-remediable factors included atypical presentation (31.3%) and the patients' inability to provide a history (31.3%). Most errors (75%) involved multiple factors. Major harm was associated with 34/209 (16.3%) of reported incidents. CONCLUSIONS: Most diagnostic errors in ED appeared to relate to common disease conditions. While sustaining diagnostic error reporting programmes might be challenging, our analysis reveals the potential value of such systems in identifying targets for improving patient safety in the ED.

Comparison of upper lip bite test and ratio of height to thyromental distance with other airway assessment tests for predicting difficult endotracheal intubation.

BACKGROUND: Various anatomical measurements and noninvasive clinical tests, singly or in various combinations can be performed to predict difficult intubation. Upper lip bite test (ULBT) and ratio of height to thyromental distance (RHTMD) are claimed to have high predictability. Hence, we have conducted this study to compare the predictive value of ULBT and RHTMD with the following parameters: Mallampati grading, inter-incisor gap, thyromental distance, sternomental distance, head and neck movements, and horizontal length of mandible for predicting difficult intubation. MATERIALS AND METHODS: In this single blinded, prospective, observational study involving 170 adult patients of either sex belonging to American Society of Anesthesiologists physical Status I-III scheduled to undergo general anesthesia were recruited. All patients were subjected to the preoperative airway assessment and, the above parameters were recorded correlated with Cormack and Lehane grade and analyzed. The number of intubation attempts and use of intubation aids were also noted. RESULTS: ULBT and RHTMD had highest sensitivity (96.64%, 90.72%), specificity (82.35%, 80.39%), positive predictive value (92.74%, 91.53%), and negative predictive value (91.3%, 78.8%), respectively, compared to other parameters. While odds ratio and likelihood ratio >1 for all the tests. CONCLUSION: ULBT can be used as a simple bedside screening test for prediction of difficult intubation, but it should be combined with other airway assessment tests for better airway predictability. RHTMD can also be used as an acceptable alternative.

Effect of erythropoietin and transfusion threshold on neurological recovery after traumatic brain injury: a randomized clinical trial.

IMPORTANCE: There is limited information about the effect of erythropoietin or a high hemoglobin transfusion threshold after a traumatic brain injury. OBJECTIVE: To compare the effects of erythropoietin and 2 hemoglobin transfusion thresholds (7 and 10 g/dL) on neurological recovery after traumatic brain injury. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial of 200 patients (erythropoietin, n = 102; placebo, n = 98) with closed head injury who were unable to follow commands and were enrolled within 6 hours of injury at neurosurgical intensive care units in 2 US level I trauma centers between May 2006 and August 2012. The study used a factorial design to test whether erythropoietin would fail to improve favorable outcomes by 20% and whether a hemoglobin transfusion threshold of greater than 10 g/dL would increase favorable outcomes without increasing complications. Erythropoietin or placebo was initially dosed daily for 3 days and then weekly for 2 more weeks (n = 74) and then the 24- and 48-hour doses were stopped for the remainder of the patients (n = 126). There were 99 patients assigned to a hemoglobin transfusion threshold of 7 g/dL and 101 patients assigned to 10 g/dL. INTERVENTIONS: Intravenous erythropoietin (500 IU/kg per dose) or saline. Transfusion threshold maintained with packed red blood cells. MAIN OUTCOMES AND MEASURES: Glasgow Outcome Scale score dichotomized as favorable (good recovery and moderate disability) or unfavorable (severe disability, vegetative, or dead) at 6 months postinjury. RESULTS: There was no interaction between erythropoietin and hemoglobin transfusion threshold. Compared with placebo (favorable outcome rate: 34/89 [38.2%; 95% CI, 28.1% to 49.1%]), both erythropoietin groups were futile (first dosing regimen: 17/35 [48.6%; 95% CI, 31.4% to 66.0%], P = .13; second dosing regimen: 17/57 [29.8%; 95% CI, 18.4% to 43.4%], P < .001). Favorable outcome rates were 37/87 (42.5%) for the hemoglobin transfusion threshold of 7 g/dL and 31/94 (33.0%) for 10 g/dL (95% CI for the difference, -0.06 to 0.25, P = .28). There was a higher incidence of thromboembolic events for the transfusion threshold of 10 g/dL (22/101 [21.8%] vs 8/99 [8.1%] for the threshold of 7 g/dL, odds ratio, 0.32 [95% CI, 0.12 to 0.79], P = .009). CONCLUSIONS AND RELEVANCE: In patients with closed head injury, neither the administration of erythropoietin nor maintaining hemoglobin concentration of greater than 10 g/dL resulted in improved neurological outcome at 6 months. The transfusion threshold of 10 g/dL was associated with a higher incidence of adverse events. These findings do not support either approach in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00313716.

Role of Non-Thermal Plasma in Fusarium Inactivation and Mycotoxin Decontamination.

Fusarium spp. is a well-studied pathogen with the potential to infect cereals and reduce the yield to maximum if left unchecked. For decades, different control treatments have been tested against different Fusarium spp. and for reducing the mycotoxins they produce and are well documented. Some treatments also involved integrated pest management (IPM) strategies against Fusarium spp. control and mycotoxin degradation produced by them. In this review article, we compiled different control strategies against different Fusarium spp. In addition, special focus is given to the non-thermal plasma (NTP) technique used against Fusarium spp. inactivation. In a separate group, we compiled the literature about the use of NTP in the decontamination of mycotoxins produced by Fusarium spp., and highlighted the possible mechanisms of mycotoxin degradation by NTP. In this review, we concluded that although NTP is an effective treatment, it is a nice area and needs further research. The possibility of a prospective novel IPM strategy against Fusarium spp. is also proposed.

Crucial Business Model Elements for Medical Device Startup Companies in Emerging Markets.

OBJECTIVES: Medical devices that suit the needs and challenges of low- and middle-income countries are desperately needed. To provide sustainable access to such devices, business approaches must be developed to meet the demands of individual economic, healthcare, and innovation ecosystems. Currently, there is a gap in the literature regarding business models for medical devices in low- and middle-income countries. METHODS: A multimodal approach using literature review and key informant interviews was performed to determine critical components of business models for medical device organizations operating in LMICs, specifically focusing on models in emerging markets. RESULTS: The search resulted in 4,674 articles, of which 31 were determined to be relevant and were reviewed. Additional sources included 1 government website, 5 nongovernmental organization websites, 2 private enterprises, and 6 publicly available, non-peer reviewed websites and 1 video. From these sources, four major criteria were found to be necessary for successful development of medical device business models in emerging markets: value proposition, partnerships, strategic pricing, and funding models. CONCLUSIONS: Innovators must custom tailor their business model when implementing these elements to the regulatory, cultural, and economic landscapes of each setting. This will improve access to safer, affordable medical care and successfully bring innovative technologies to emerging markets.

The Evolving Landscape of Medical Device Regulation in East, Central, and Southern Africa.

Effective regulatory frameworks, harmonized to international standards, are critical to expanding access to quality medical devices in low- and middle-income countries. This review provides a summary of the state of medical device regulation in the 14 member countries of the College of Surgeons of East, Central, and Southern Africa (COSECSA) and South Africa. Countries were categorized according to level of regulatory establishment, which was found to be positively correlated to gross domestic product (GDP; rs=0.90) and years of freedom from colonization (rs=0.60), and less positively correlated to GDP per capita (rs=0.40). Although most countries mandate medical device regulation in national legislation, few employ all the guidelines set forth by the World Health Organization. A streamlined regulatory process across African nations would simplify this process for innovators seeking to bring medical devices to the African market, thereby increasing patient access to safe medical devices.

Composted Municipal Green Waste Infused with Biocontrol Agents to Control Plant Parasitic Nematodes-A Review.

The last few years have witnessed the emergence of alternative measures to control plant parasitic nematodes (PPNs). We briefly reviewed the potential of compost and the direct or indirect roles of soil-dwelling organisms against PPNs. We compiled and assessed the most intensively researched factors of suppressivity. Municipal green waste (MGW) was identified and profiled. We found that compost, with or without beneficial microorganisms as biocontrol agents (BCAs) against PPNs, were shown to have mechanisms for the control of plant parasitic nematodes. Compost supports a diverse microbiome, introduces and enhances populations of antagonistic microorganisms, releases nematicidal compounds, increases the tolerance and resistance of plants, and encourages the establishment of a "soil environment" that is unsuitable for PPNs. Our compilation of recent papers reveals that while the scope of research on compost and BCAs is extensive, the role of MGW-based compost (MGWC) in the control of PPNs has been given less attention. We conclude that the most environmentally friendly and long-term, sustainable form of PPN control is to encourage and enhance the soil microbiome. MGW is a valuable resource material produced in significant amounts worldwide. More studies are suggested on the use of MGWC, because it has a considerable potential to create and maintain soil suppressivity against PPNs. To expand knowledge, future research directions shall include trials investigating MGWC, inoculated with BCAs.

Convalescent plasma associates with reduced mortality and improved clinical trajectory in patients hospitalized with COVID-19.

BACKGROUNDEvidence supporting convalescent plasma (CP), one of the first investigational treatments for coronavirus disease 2019 (COVID-19), has been inconclusive, leading to conflicting recommendations. The primary objective was to perform a comparative effectiveness study of CP for all-cause, in-hospital mortality in patients with COVID-19.METHODSThe multicenter, electronic health records-based, retrospective study included 44,770 patients hospitalized with COVID-19 in one of 176 HCA Healthcare-affiliated community hospitals. Coarsened exact matching (1:k) was employed, resulting in a sample of 3774 CP and 10,687 comparison patients.RESULTSExamination of mortality using a shared frailty model, controlling for concomitant medications, date of admission, and days from admission to transfusion, demonstrated a significant association of CP with lower mortality risk relative to the comparison group (adjusted hazard ratio [aHR] = 0.71; 95% CI, 0.59-0.86; P < 0.001). Examination of patient risk trajectories, represented by 400 clinico-demographic features from our real-time risk model (RTRM), indicated that patients who received CP recovered more quickly. The stratification of days to transfusion revealed that CP within 3 days after admission, but not within 4 to 7 days, was associated with a significantly lower mortality risk (aHR = 0.53; 95% CI, 0.47-0.60; P < 0.001). CP serology level was inversely associated with mortality when controlling for its interaction with days to transfusion (HR = 0.998; 95% CI, 0.997-0.999; P = 0.013), yet it did not reach univariable significance.CONCLUSIONSThis large, diverse, multicenter cohort study demonstrated that CP, compared with matched controls, is significantly associated with reduced risk of in-hospital mortality. These observations highlight the utility of real-world evidence and suggest the need for further evaluation prior to abandoning CP as a viable therapy for COVID-19.FUNDINGThis research was supported in whole by HCA Healthcare and/or an HCA Healthcare-affiliated entity, including Sarah Cannon and Genospace.