Clinical Utility of the Risk Analysis Index as a Prospective Frailty Screening Tool within a Multi-practice, Multi-hospital Integrated Healthcare System.

OBJECTIVE: The goal of this project was to first address barriers to implementation of the Risk Analysis Index (RAI) within a large, multi-hospital, integrated healthcare delivery system, and to subsequently demonstrate its utility for identifying at-risk surgical patients. BACKGROUND: Prior studies demonstrate the validity of the RAI for evaluating preoperative frailty, but they have not demonstrated the feasibility of its implementation within routine clinical practice. METHODS: Implementation of the RAI as a frailty screening instrument began as a quality improvement initiative at the University of Pittsburgh Medical Center in July 2016. RAI scores were collected within a REDCap survey instrument integrated into the outpatient electronic health record and then linked to information from additional clinical datasets. NSQIP-eligible procedures were queried within 90 days following the RAI, and the association between RAI and postoperative mortality was evaluated using logistic regression and Cox proportional hazards models. Secondary outcomes such as inpatient length of stay and readmissions were also assessed. RESULTS: RAI assessments were completed on 36,261 unique patients presenting to surgical clinics across five hospitals from July 1 to December 31, 2016, and 8,172 of these underwent NSQIP-eligible surgical procedures. The mean RAI score was 23.6 (SD 11.2), the overall 30-day and 180-day mortality after surgery was 0.7% and 2.6%, respectively, and the median time required to collect the RAI was 33 [IQR 23-53] seconds. Overall clinic compliance with the recommendation for RAI assessment increased from 58% in the first month of the study period to 84% in the sixth and final month. RAI score was significantly associated with risk of death (HR=1.099 [95% C.I.: 1.091 - 1.106], p < 0.001). At an RAI cutoff of ≥37, the positive predictive values for 30- and 90-day readmission were 14.8% and 26.2%, respectively, and negative predictive values were 91.6% and 86.4%, respectively. CONCLUSIONS: The RAI frailty screening tool can be efficiently implemented within multi-specialty, multi-hospital healthcare systems. In the context of our findings and given the value of the RAI in predicting adverse postoperative outcomes, health systems should consider implementing frailty screening within surgical clinics.

Very low rate of patient-related adverse events associated with the use of intraoperative cell salvage.

BACKGROUND: The rate of patient-related clinical adverse events (AEs) associated with the use of intraoperative cell salvage (ICS) was analyzed. STUDY DESIGN AND METHODS: The perfusion service and electronic risk management databases in a nine-hospital regional health care system were reviewed over an approximately 11-year period. The number of ICS cases performed during this period and basic patient demographics were also extracted. RESULTS: There were 43,198 patients for whom ICS was utilized during the study period. Recovered blood was returned to 33,351 (77.2%) patients. Electronic comments on the ICS procedure were found in 2348 of 33,351 (7.0%) cases. The vast majority of comments (2203/2348, 93.8%) described minor events that did not lead to patient-related AEs such as the surgeon requested higher than normal suction pressure or that no RBCs were returned. Only 144 of 2348 (6.1%) of the comments described procedural or equipment-related events or potential AEs. From these comments two potential AEs were identified: the first was a post-Cesarean section patient who became acutely tachycardic, hypertensive, and dyspneic with rigors. The second was a patient with postpartum hemorrhage who experienced acute dyspnea and hypotension. Both patients were rapidly stabilized and discharged from the hospital shortly thereafter without further complications. It is unclear if these events were caused by ICS reinfusion. No air emboli were reported. The overall rate of patient-related AEs associated with ICS reinfusion was between 0 and 2 per 33,351 (0%-0.006%). CONCLUSIONS: The use of ICS is safe with a very low rate of patient-related AEs.

Electronic enhancements to blood ordering reduce component waste.

BACKGROUND: The effect on component wastage after enhancing the clinician's ability to order blood products in the computerized physician order entry (CPOE) system was investigated in a multihospital network. METHODS: A novel field was added to the CPOE of eight hospitals within a health care system allowing the physician to reserve a red blood cell (RBC) unit for transfusion at a later time. Simultaneously, an electronic means of communication with the blood bank was implemented requiring the nurse to ensure that the patient was prepared for the transfusion before a product could be issued. The wastage rates in the 12 months after these electronic enhancements (Phase 2) was compared to the preceding 19 months of a non-CPOE-based waste reduction campaign (Phase 1) and to the 24 months before the campaign (baseline period). RESULTS: There were significant reductions in platelet (PLT) waste between the baseline period and Phase 1 (p < 0.05) and between Phase 2 and both Phase 1 and the baseline period (p < 0.05). The annual systemwide cost savings in wasted PLTs between the baseline period and Phase 2 was approximately $123,300. RBC waste was significantly reduced between Phase 2 and both Phase 1 and the baseline period (p < 0.05). Cryoprecipitate waste was reduced between Phase 2 and the baseline period (p < 0.05), while plasma waste did not change between the three periods. CONCLUSIONS: Implementing a multifaceted approach to waste reduction led to a significant reduction in wastage for RBCs, PLTs, and cryoprecipitate.

Association of Routine Preoperative Frailty Assessment With 1-Year Postoperative Mortality.

Importance: Patient frailty is a known risk factor for adverse outcomes following surgery, but data are limited regarding whether systemwide interventions related to frailty are associated with improved patient outcomes. Objective: To evaluate whether a frailty screening initiative (FSI) is associated with reduced late-term mortality after elective surgery. Design, Setting, and Participants: This quality improvement study with an interrupted time series analysis used data from a longitudinal cohort of patients in a multihospital, integrated health care system in the US. Beginning in July 2016, surgeons were incentivized to measure frailty with the Risk Analysis Index (RAI) for all patients considering elective surgery. Implementation of the BPA occurred in February 2018. The cutoff for data collection was May 31, 2019. Analyses were conducted between January and September 2022. Exposures: The exposure of interest was an Epic Best Practice Alert (BPA) used to identify patients with frailty (RAI ≥42) and prompt surgeons to document a frailty-informed shared decision-making process and consider additional evaluation by a multidisciplinary presurgical care clinic or the primary care physician. Main Outcomes and Measures: The primary outcome was 365-day mortality after the elective surgical procedure. Secondary outcomes included 30-day and 180-day mortality as well as the proportion of patients referred for additional evaluation based on documented frailty. Results: A total of 50 463 patients with at least 1 year of postsurgical follow-up (22 722 before intervention implementation and 27 741 after) were included (mean [SD] age, 56.7 [16.0] y; 57.6% women). Demographic characteristics, RAI score, and operative case mix, as defined by Operative Stress Score, were similar between time periods. After BPA implementation, the proportion of frail patients referred to a primary care physician and presurgical care clinic increased significantly (9.8% vs 24.6% and 1.3% vs 11.4%, respectively; both P < .001). Multivariable regression analysis demonstrated an 18% reduction in the odds of 1-year mortality (0.82; 95% CI, 0.72-0.92; P < .001). Interrupted time series models demonstrated a significant slope change in the rate of 365-day mortality from 0.12% in the preintervention period to -0.04% in the postintervention period. Among patients triggering the BPA, estimated 1-year mortality changed by -4.2% (95% CI, -6.0% to -2.4%). Conclusions and Relevance: This quality improvement study found that implementation of an RAI-based FSI was associated with increased referrals of frail patients for enhanced presurgical evaluation. These referrals translated to a survival advantage among frail patients of similar magnitude to those observed in a Veterans Affairs health care setting, providing further evidence for both the effectiveness and generalizability of FSIs incorporating the RAI.

Increasing Quality and Frequency of Goals-of-Care Documentation in the Highest-Risk Surgical Candidates: One-Year Results of the Surgical Pause Program.

Patient values may be obscured when decisions are made under the circumstances of constrained time and limited counseling. The objective of this study was to determine if a multidisciplinary review aimed at ensuring goal-concordant treatment and perioperative risk assessment in high-risk orthopaedic trauma patients would increase the quality and frequency of goals-of-care documentation without increasing the rate of adverse events. Methods: We prospectively analyzed a longitudinal cohort of adult patients treated for traumatic orthopaedic injuries that were neither life- nor limb-threatening between January 1, 2020, and July 1, 2021. A rapid multidisciplinary review termed a "surgical pause" (SP) was available to those who were ≥80 years old, were nonambulatory or had minimal ambulation at baseline, and/or resided in a skilled nursing facility, as well as upon clinician request. Metrics analyzed include the proportion and quality of goals-of-care documentation, rate of return to the hospital, complications, length of stay, and mortality. Statistical analysis utilized the Kruskal-Wallis rank and Wilcoxon rank-sum tests for continuous variables and the likelihood-ratio chi-square test for categorical variables. Results: A total of 133 patients were either eligible for the SP or referred by a clinician. Compared with SP-eligible patients who did not undergo an SP, patients who underwent an SP more frequently had goals-of-care notes identified (92.4% versus 75.0%, p = 0.014) and recorded in the appropriate location (71.2% versus 27.5%, p < 0.001), and the notes were more often of high quality (77.3% versus 45.0%, p < 0.001). Mortality rates were nominally higher among SP patients, but these differences were not significant (10.6% versus 5.0%, 5.1% versus 0.0%, and 14.3% versus 7.9% for in-hospital, 30-day, and 90-day mortality, respectively; p > 0.08 for all). Conclusions: The pilot program indicated that an SP is a feasible and effective means of increasing the quality and frequency of goals-of-care documentation in high-risk operative candidates whose traumatic orthopaedic injuries are neither life- nor limb-threatening. This multidisciplinary program aims for goal-concordant treatment plans that minimize modifiable perioperative risks. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Launching a comparative effectiveness adaptive platform trial of monoclonal antibodies for COVID-19 in 21 days.

Outpatient treatments that limit progression to severe coronavirus disease 2019 (COVID-19) are of vital importance to optimise patient outcomes and public health. Monoclonal antibodies (mAb) demonstrated ability to decrease hospitalizations in randomized, clinical trials. However, there are many barriers to mAb treatment such as patient access and clinician education. There are no data comparing efficacy or safety of available mAbs. We sought to rapidly launch an adaptive platform trial with the goals of enhancing access to treatment, regardless of geography and socioeconomic status, and evaluating comparative efficacy and safety of available mAbs. Within 21 days from idea genesis, we allocated mAb treatment to all patients within the context of this clinical trial. Within 2 months, we closed the gap of the likelihood of receiving mAb, conditional on background positivity rate, between Black and White patients (Black patients 0.238; White patients 0.241). We describe trial infrastructure, lessons learned, and future directions for a culture of learning while doing.

Association of Subcutaneous or Intravenous Administration of Casirivimab and Imdevimab Monoclonal Antibodies With Clinical Outcomes in Adults With COVID-19.

Importance: Monoclonal antibody (mAb) treatment decreases hospitalization and death in high-risk outpatients with mild to moderate COVID-19; however, only intravenous administration has been evaluated in randomized clinical trials of treatment. Subcutaneous administration may expand outpatient treatment capacity and qualified staff available to administer treatment, but the association with patient outcomes is understudied. Objectives: To evaluate whether subcutaneous casirivimab and imdevimab treatment is associated with reduced 28-day hospitalization and death compared with nontreatment among mAb-eligible patients and whether subcutaneous casirivimab and imdevimab treatment is clinically and statistically similar to intravenous casirivimab and imdevimab treatment. Design, Setting, and Participants: This prospective cohort study evaluated high-risk outpatients in a learning health system in the US with mild to moderate COVID-19 symptoms from July 14 to October 26, 2021, who were eligible for mAb treatment under emergency use authorization. A nontreated control group of eligible patients was also studied. Exposures: Subcutaneous injection or intravenous administration of the combined single dose of 600 mg of casirivimab and 600 mg of imdevimab. Main Outcomes and Measures: The primary outcome was the 28-day adjusted risk ratio or adjusted risk difference for hospitalization or death. Secondary outcomes included 28-day adjusted risk ratios and differences in hospitalization, death, a composite end point of emergency department admission and hospitalization, and rates of adverse events. Among 1959 matched adults with mild to moderate COVID-19, 969 patients (mean [SD] age, 53.8 [16.7] years; 547 women [56.4%]) who received casirivimab and imdevimab subcutaneously had a 28-day rate of hospitalization or death of 3.4% (22 of 653 patients) compared with 7.0% (92 of 1306 patients) in nontreated controls (risk ratio, 0.48; 95% CI, 0.30-0.80; P = .002). Among 2185 patients treated with subcutaneous (n = 969) or intravenous (n = 1216; mean [SD] age, 54.3 [16.6] years; 672 women [54.4%]) casirivimab and imdevimab, the 28-day rate of hospitalization or death was 2.8% vs 1.7%, which resulted in an adjusted risk difference of 1.5% (95% CI, -0.6% to 3.5%; P = .16). Among all infusion patients, there was no difference in intensive care unit admission (adjusted risk difference, 0.7%; 95% CI, -3.5% to 5.0%) or need for mechanical ventilation (adjusted risk difference, 0.2%; 95% CI, -5.8% to 5.5%). Conclusions and Relevance: In this cohort study of high-risk outpatients with mild to moderate COVID-19 symptoms, subcutaneously administered casirivimab and imdevimab was associated with reduced hospitalization and death when compared with no treatment. These results provide preliminary evidence of potential expanded use of subcutaneous mAb treatment, particularly in areas that are facing treatment capacity and/or staffing shortages.

The comparative effectiveness of COVID-19 monoclonal antibodies: A learning health system randomized clinical trial.

BACKGROUND: Monoclonal antibodies (mAb) that neutralize SARS-CoV-2 decrease hospitalization and death compared to placebo in patients with mild to moderate COVID-19; however, comparative effectiveness is unknown. We report the comparative effectiveness of bamlanivimab, bamlanivimab-etesevimab, and casirivimab-imdevimab. METHODS: A learning health system platform trial in a U.S. health system enrolled patients meeting mAb Emergency Use Authorization criteria. An electronic health record-embedded application linked local mAb inventory to patient encounters and provided random mAb allocation. Primary outcome was hospital-free days to day 28. Primary analysis was a Bayesian model adjusting for treatment location, age, sex, and time. Inferiority was defined as 99% posterior probability of an odds ratio < 1. Equivalence was defined as 95% posterior probability the odds ratio is within a given bound. FINDINGS: Between March 10 and June 25, 2021, 1935 patients received treatment. Median hospital-free days were 28 (IQR 28, 28) for each mAb. Mortality was 0.8% (1/128), 0.8% (7/885), and 0.7% (6/922) for bamlanivimab, bamlanivimab-etesevimab, and casirivimab-imdevimab, respectively. Relative to casirivimab-imdevimab (n = 922), median adjusted odds ratios were 0.58 (95% credible interval [CI] 0.30-1.16) and 0.94 (95% CI 0.72-1.24) for bamlanivimab (n = 128) and bamlanivimab-etesevimab (n = 885), respectively. These odds ratios yielded 91% and 94% probabilities of inferiority of bamlanivimab versus bamlanivimab-etesevimab and casirivimab-imdevimab, and an 86% probability of equivalence between bamlanivimab-etesevimab and casirivimab-imdevimab. INTERPRETATION: Among patients with mild to moderate COVID-19, bamlanivimab-etesevimab or casirivimab-imdevimab treatment resulted in 86% probability of equivalence. No treatment met prespecified criteria for statistical equivalence. Median hospital-free days to day 28 were 28 (IQR 28, 28) for each mAb. FUNDING AND REGISTRATION: This work received no external funding. The U.S. government provided the reported mAb. This trial is registered at ClinicalTrials.gov, NCT04790786.

Effectiveness of Casirivimab-Imdevimab and Sotrovimab During a SARS-CoV-2 Delta Variant Surge: A Cohort Study and Randomized Comparative Effectiveness Trial.

Importance: The effectiveness of monoclonal antibodies (mAbs), casirivimab-imdevimab and sotrovimab, is unknown in patients with mild to moderate COVID-19 caused by the SARS-CoV-2 Delta variant. Objective: To evaluate the effectiveness of mAb against the Delta variant compared with no mAb treatment and to ascertain the comparative effectiveness of casirivimab-imdevimab and sotrovimab. Design, Setting, and Participants: This study comprised 2 parallel studies: (1) a propensity score-matched cohort study of mAb treatment vs no mAb treatment and (2) a randomized comparative effectiveness trial of casirivimab-imdevimab and sotrovimab. The cohort consisted of patients who received mAb treatment at the University of Pittsburgh Medical Center outpatient infusion centers and emergency departments from July 14 to September 29, 2021. Participants were patients with a positive SARS-CoV-2 test result who were eligible to receive mAbs according to emergency use authorization criteria. Exposure: For the trial, patients were randomized to either intravenous casirivimab-imdevimab or sotrovimab according to a system therapeutic interchange policy. Main Outcomes and Measures: For the cohort study, risk ratio (RR) estimates for the primary outcome of hospitalization or death by 28 days were compared between mAb treatment and no mAb treatment using propensity score-matched models. For the comparative effectiveness trial, the primary outcome was hospital-free days (days alive and free of hospitalization) within 28 days after mAb treatment, where patients who died were assigned -1 day in a bayesian cumulative logistic model adjusted for treatment location, age, sex, and time. Inferiority was defined as a 99% posterior probability of an odds ratio (OR) less than 1. Equivalence was defined as a 95% posterior probability that the OR was within a given bound. Results: A total of 3069 patients (1023 received mAb treatment: mean [SD] age, 53.2 [16.4] years; 569 women [56%]; 2046 had no mAb treatment: mean [SD] age, 52.8 [19.5] years; 1157 women [57%]) were included in the prospective cohort study, and 3558 patients (mean [SD] age, 54 [18] years; 1919 women [54%]) were included in the randomized comparative effectiveness trial. In propensity score-matched models, mAb treatment was associated with reduced risk of hospitalization or death (RR, 0.40; 95% CI, 0.28-0.57) compared with no treatment. Both casirivimab-imdevimab (RR, 0.31; 95% CI, 0.20-0.50) and sotrovimab (RR, 0.60; 95% CI, 0.37-1.00) were associated with reduced hospitalization or death compared with no mAb treatment. In the clinical trial, 2454 patients were randomized to receive casirivimab-imdevimab and 1104 patients were randomized to receive sotrovimab. The median (IQR) hospital-free days were 28 (28-28) for both mAb treatments, the 28-day mortality rate was less than 1% (n = 12) for casirivimab-imdevimab and less than 1% (n = 7) for sotrovimab, and the hospitalization rate by day 28 was 12% (n = 291) for casirivimab-imdevimab and 13% (n = 140) for sotrovimab. Compared with patients who received casirivimab-imdevimab, those who received sotrovimab had a median adjusted OR for hospital-free days of 0.88 (95% credible interval, 0.70-1.11). This OR yielded 86% probability of inferiority for sotrovimab vs casirivimab-imdevimab and 79% probability of equivalence. Conclusions and Relevance: In this propensity score-matched cohort study and randomized comparative effectiveness trial, the effectiveness of casirivimab-imdevimab and sotrovimab against the Delta variant was similar, although the prespecified criteria for statistical inferiority or equivalence were not met. Both mAb treatments were associated with a reduced risk of hospitalization or death in nonhospitalized patients with mild to moderate COVID-19 caused by the Delta variant. Trial Registration: ClinicalTrials.gov Identifier: NCT04790786.

SafeNET: Initial development and validation of a real-time tool for predicting mortality risk at the time of hospital transfer to a higher level of care.

BACKGROUND: Processes for transferring patients to higher acuity facilities lack a standardized approach to prognostication, increasing the risk for low value care that imposes significant burdens on patients and their families with unclear benefits. We sought to develop a rapid and feasible tool for predicting mortality using variables readily available at the time of hospital transfer. METHODS AND FINDINGS: All work was carried out at a single, large, multi-hospital integrated healthcare system. We used a retrospective cohort for model development consisting of patients aged 18 years or older transferred into the healthcare system from another hospital, hospice, skilled nursing or other healthcare facility with an admission priority of direct emergency admit. The cohort was randomly divided into training and test sets to develop first a 54-variable, and then a 14-variable gradient boosting model to predict the primary outcome of all cause in-hospital mortality. Secondary outcomes included 30-day and 90-day mortality and transition to comfort measures only or hospice care. For model validation, we used a prospective cohort consisting of all patients transferred to a single, tertiary care hospital from one of the 3 referring hospitals, excluding patients transferred for myocardial infarction or maternal labor and delivery. Prospective validation was performed by using a web-based tool to calculate the risk of mortality at the time of transfer. Observed outcomes were compared to predicted outcomes to assess model performance. The development cohort included 20,985 patients with 1,937 (9.2%) in-hospital mortalities, 2,884 (13.7%) 30-day mortalities, and 3,899 (18.6%) 90-day mortalities. The 14-variable gradient boosting model effectively predicted in-hospital, 30-day and 90-day mortality (c = 0.903 [95% CI:0.891-0.916]), c = 0.877 [95% CI:0.864-0.890]), and c = 0.869 [95% CI:0.857-0.881], respectively). The tool was proven feasible and valid for bedside implementation in a prospective cohort of 679 sequentially transferred patients for whom the bedside nurse calculated a SafeNET score at the time of transfer, taking only 4-5 minutes per patient with discrimination consistent with the development sample for in-hospital, 30-day and 90-day mortality (c = 0.836 [95%CI: 0.751-0.921], 0.815 [95% CI: 0.730-0.900], and 0.794 [95% CI: 0.725-0.864], respectively). CONCLUSIONS: The SafeNET algorithm is feasible and valid for real-time, bedside mortality risk prediction at the time of hospital transfer. Work is ongoing to build pathways triggered by this score that direct needed resources to the patients at greatest risk of poor outcomes.

Impact of Bamlanivimab Monoclonal Antibody Treatment on Hospitalization and Mortality Among Nonhospitalized Adults With Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

BACKGROUND: Monoclonal antibody treatment may prevent complications of coronavirus disease 2019 (COVID-19). We sought to quantify the impact of bamlanivimab monoclonal antibody monotherapy on hospitalization and mortality among outpatients at high risk of COVID-19 complications. METHODS: In this observational study we compared outpatients who received bamlanivimab monoclonal antibody from December 9, 2020 to March 3, 2021 to nontreated patients with a positive polymerase chain reaction or antigen test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the same period who were eligible for monoclonal antibody treatment. The primary outcome was 28-day hospitalization or all-cause mortality, and the secondary outcome was hospitalization or emergency department visit without hospitalization. The risk-adjusted odds of study outcomes comparing bamlanivimab treated and untreated patients was determined using 1:5 propensity matching and multivariable logistic regression. RESULTS: Among 232 patients receiving bamlanivimab matched with 1160 comparator patients, the mean age was 67 years, 56% were female, and 196 (14%) of patients experienced hospitalization or mortality. After adjustment for propensity to receive treatment, bamlanivimab treatment was associated with a significantly reduced risk-adjusted odds of hospitalization or mortality within 28 days (odds ratio [OR], 0.40; 95% confidence interval [95% CI], 0.24-0.69; P < .001). Bamlanivimab treatment was also associated with a significantly lower risk adjusted odds of hospitalization or emergency department visit without hospitalization (OR, 0.54; 95% CI, 0.35-0.82; P = .004). The results were most strongly associated with patients age 65 years and older. CONCLUSIONS: Bamlanivimab monoclonal antibody monotherapy was associated with reduced hospitalizations and mortality within 28 days among outpatients with mild to moderate COVID-19.Use of bamlanivimab monotherapy for outpatients with mild to moderate COVID-19 infection was associated with reductions in hospitalizations and mortality within 28 days. Benefit was strongest in those age 65 years or older.

The UPMC OPTIMISE-C19 (OPtimizing Treatment and Impact of Monoclonal antIbodieS through Evaluation for COVID-19) trial: a structured summary of a study protocol for an open-label, pragmatic, comparative effectiveness platform trial with response-adaptive randomization.

OBJECTIVES: The primary objective is to evaluate the comparative effectiveness of COVID-19 specific monoclonal antibodies (mABs) with US Food and Drug Administration (FDA) Emergency Use Authorization (EUA), alongside UPMC Health System efforts to increase patient access to these mABs. TRIAL DESIGN: Open-label, pragmatic, comparative effectiveness platform trial with response-adaptive randomization PARTICIPANTS: We will evaluate patients who meet the eligibility criteria stipulated by the COVID-19 mAB EUAs who receive mABs within the UPMC Health System, including infusion centers and emergency departments. EUA eligibility criteria include patients with mild to moderate COVID-19, <10 days of symptoms, and who are at high risk for progressing to severe COVID-19 and/or hospitalization (elderly, obese, and/or with specific comorbidities). The EUA criteria exclude patients who require oxygen for the treatment of COVID-19 and patients already hospitalized for the treatment of COVID-19. We will use data collected for routine clinical care, including data entered into the electronic medical record and from follow-up calls. INTERVENTION AND COMPARATOR: The interventions are the COVID-19 specific mABs authorized by the EUAs. All aspects of mAB treatment, including eligibility criteria, dosing, and post-infusion monitoring, are as per the EUAs. As a comparative effectiveness trial, all patients receive mAB treatment, and the interventions are compared against each other. When U.S. government mAB policies change (e.g., FDA grants or revokes EUAs), UPMC Health System policies and the evaluated mAB interventions will accordingly change. From November 2020 to February 2021, FDA issued EUAs for three mAB treatments (bamlanivimab; bamlanivimab and etesevimab; and casirivimab and imdevimab), and at trial launch on March 10, 2021 we evaluated all three. Due to a sustained increase in SARS-CoV-2 variants in the United States resistant to bamlanivimab administered alone, on March 24, 2021 the U.S. Government halted distribution of bamlanivimab alone, and UPMC accordingly halted bamlanivimab monotherapy on March 31, 2021. On April 16, 2021, FDA revoked the EUA for bamlanivimab monotherapy. At the time of manuscript submission, we are therefore evaluating the two mAB treatments authorized by EUAs (bamlanivimab and etesevimab; and casirivimab and imdevimab). MAIN OUTCOMES: The primary outcome is total hospital free days (HFD) at 28 days after mAB administration, calculated as 28 minus the number of days during the index stay (if applicable - e.g., for patients admitted to hospital after mAB administration in the emergency department) minus the number of days readmitted during the 28 days after treatment. This composite endpoint captures the number of days from the day of mAB administration to the 28 days thereafter, during which the patient is alive and free of hospitalization. Death within 28 days is recorded as -1 HFD, as the worst outcome. RANDOMISATION: We will start with equal allocation. Due to uncertainty in sample size, we will use a Bayesian adaptive design and response adaptive randomization to ensure ability to provide statistical inference despite variable sample size. When mABs are ordered by UPMC physicians as a generic referral order, the order is filled by UPMC pharmacy via therapeutic interchange. OPTIMISE-C19 provides the therapeutic interchange via random allocation. Infusion center operations teams and pharmacists use a mAB assignment application embedded in the electronic medical record to determine the random allocation. BLINDING (MASKING): This trial is open-label. However, outcome assessors conducting follow-up calls at day 28 are blinded to mAB assignment, and investigators are blinded to by-mAB aggregate outcome data until a statistical platform trial conclusion is reached. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Sample size will be determined by case volume throughout the course of the pandemic, supply of FDA authorized mABs, and by that needed to reach a platform trial conclusion of inferiority, superiority, or futility of a given mAB. The trial will continue as long as more than one mAB type is available under EUA, and their comparative effectiveness is uncertain. TRIAL STATUS: Protocol Version 1.0, February 24, 2021. Recruitment began March 10, 2021 and is ongoing at the time of manuscript submission. The estimated recruitment end date is February 22, 2022, though the final end date is dependent on how the pandemic evolves, mAB availability, and when final platform trial conclusions are reached. As noted above, due to U.S. Government decisions, UPMC Health System halted bamlanivimab monotherapy on March 31, 2021. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04790786 . Registered March 10, 2021 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Validation of the Risk Analysis Index for Evaluating Frailty in Ambulatory Patients.

BACKGROUND: Frailty is a marker of dependency, disability, hospitalization, and mortality in community-dwelling older adults. However, existing tools for measuring frailty are too cumbersome for rapid point-of-care assessment. The Risk Analysis Index (RAI) of frailty is validated in surgical populations, but its performance outside surgical populations is unknown. OBJECTIVE: Validate the RAI in ambulatory patients. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of outpatient surgical clinics within the University of Pittsburgh Medical Center Healthcare System between July 1, 2016, and December 31, 2016. Frailty was assessed using the RAI. Current Procedural Terminology codes following RAI assessment identified patients with and without minor office-based procedures (eg, joint injection, laryngoscopy). MAIN OUTCOMES AND MEASURES: All-cause 1-year mortality, assessed by stratified Cox proportional hazard models. RESULTS: Of 28,059 patients, 13,861 were matched to a minor, office-based procedure and 14,198 did not undergo any procedure. The mean (SD) age was 56.7 (17.2) years; women constituted 15,797 (56.3%) of the cohort. Median time (interquartile range 25th-75th percentile) to measure RAI was 30 (22-47) seconds. Mortality among the frail was two to five times that of patients with normal RAI scores. For example, the hazard ratio for frail ambulatory patients without a minor procedure was 3.69 (95% confidence interval [CI] = 2.51-5.41), corresponding to 30-, 180-, and 365-day mortality rates of 2.9%, 11.2%, and 17.4%, respectively, compared to 0.3%, 2.3%, and 4.0% among patients with normal RAI scores. Discrimination of mortality (overall, and censored at 30, 180, and 365 days) was excellent, ranging from c = 0.838 (95% CI = 0.773-0.902) for 30-day mortality after minor procedures to c = 0.909 (95% CI = 0.855-0.964) without a procedure. CONCLUSION: RAI is a valid, easily administered tool for point-of-care frailty assessment in ambulatory populations that may help clinicians and patients make better informed decisions about care choices-especially among patients considered high risk with a potentially limited life span. J Am Geriatr Soc 68:1818-1824, 2020.

Changes in blood product utilization in a seven-hospital system after the implementation of a patient blood management program: A 9-year follow-up.

OBJECTIVES: To analyze changes in red blood cell (RBC), platelet (PLT), and plasma transfusion volumes 9 years after the implementation of a multifaceted patient blood management (PBM) program across multiple hospitals. METHODS: Between fiscal years 2007 and 2015, the annual transfusion volumes for seven hospitals in a regional healthcare system were analyzed by hospital, and between 2014 and 2015, by four service lines including emergency department, intensive care unit (ICU), medical/surgical ward, and operating room at each hospital. The number of units of RBCs administered to transfused recipients on the wards and in ICUs was also enumerated. RESULTS: For these seven hospitals combined, there was a 29.9% reduction in the number of RBCs transfused between 2007 and 2015, a 24.8% reduction in plasma units, and a 25.7% reduction in PLT units. The two largest hospitals saw some of the largest reductions in RBC transfusions (40.1, 25.1%), and plasma transfusions (26.1, 33.8%), and one of those hospitals had a 49.5% reduction in PLT transfusions. Smaller-sized hospitals also had reductions in transfusion volumes, while some volumes increased at hospitals when new or expanded clinical services were introduced. The number of RBC units per transfused recipient was generally between 1.5 and 2 units on the wards and slightly higher in the ICUs. DISCUSSION: Although the overall volume of transfusions has generally decreased at each hospital site over time, the appropriateness of the administered transfusions cannot be evaluated by these data. CONCLUSION: The system-wide implementation of a PBM program has reduced transfusion volumes.

The effect of automated alerts on preoperative anemia management.

OBJECTIVES: This study evaluated the role of an automated anemia notification system that alerted providers about anemic pre-operative patients. METHODS: After scheduling surgery, the alert program continuously searched the patient's laboratory data for hemoglobin value(s) in the medical record. When an anemic patient according to the World Health Oganization's criteria was identified, an email was sent to the patient's surgeon, and/or assistant, and/or patient's primary care physician suggesting that the anemia be managed before surgery. RESULTS: Thirteen surgeons participated in this pilot study. In 11 months, there were 70 pre-surgery anemia alerts generated on 69 patients. The surgeries were 60 orthopedic, 7 thoracic, 2 general surgery, and 1 urological. The alerts were sent 15 ± 10 days before surgery. No pre-operative anemia treatment could be found in 37 of 69 (54%) patients. Some form of anemia management was found in 32 of 69 (46%) patients. Of the 23 patients who received iron, only 3 of 23 (13%) of these patients started iron shortly after the alert was generated. The alert likely resulted in the postponement of one surgery for anemia correction. DISCUSSION: Although anemia diagnosis and management can be complex, it was hoped that receipt of the alert would lead to the management of all anemic patients. Alerts are only effective if they are received and read by a healthcare provider empowered to treat the patient or to make an appropriate referral. CONCLUSIONS: Automated preoperative alerts alone are not likely to alter surgeons' anemia management practices. These alerts need to be part of a comprehensive anemia management strategy.

Transforming care at the bedside: an ambulatory model for improving the patient experience.

Transforming Care at the Bedside is a nationwide effort to design a model for improving care to hospitalized patients. With the projected growth of ambulatory services, it is increasingly important to focus on potential methods to increase patient satisfaction and care delivery improvement in the outpatient setting, as well. The authors describe the University of Pittsburgh Medical Center Hillman Cancer Center's adaptation of the Transforming Care at the Bedside care delivery improvement model to its ambulatory services arena and its promising results.